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Clinical features of polymyositis/dermatomyositis associated with silicosis and a review of the literature.

There are few reports which describe the association of polymyositis/dermatomyositis (PM/DM) and silicosis. The purpose of this study is to describe the clinical features of PM/DM associated with silicosis. We first describe clinical features of two cases and provide a review of the literature. Finally, seven patients with PM/DM associated with silicosis are retrospectively evaluated. There were one female and six males. Histological specimens were obtained by open lung biopsy in five cases and not examined in two. The mechanism of the association between silicosis and PM/DM is discussed.

Biopsy, Needle↗

Silica, silicosis and lung-cancer: results from a cohort study in the stone and quarry industry.

BACKGROUND: Workers compensated for silicosis outside the mining industry are at an increased risk of developing lung cancer. In the meta-analyses no data from Germany are involved. Furthermore, exposure data are necessary if a threshold value is to be assessed in order to reduce the risk for silicosis and also for lung cancer. METHOD: A cohort study among workers compensated for silicosis between 1988 and 2000 from the stone and quarry industry in Germany has been initiated. The cohort was followed up until the end of 2001. From all workers a detailed description of their jobs was assessed. RESULTS: Four hundred and forty workers were enrolled in the study. During the follow-up 144 workers died, compared with 74.35 expected cases based on the mortality rates of the general population from Germany, leading to a standard mortality ratio (SMR) of 1.94 (95% CI 1.63-2.28). Lung cancer was the cause of death in 16 cases (SMR 2.40; 95% CI 1.37-3.90). All workers had a peak exposure above 0.15 mg/m3, the current threshold value. The cumulative exposure was above 2 mg/m3.years and the average exposure was 0.10 mg/m3 or larger. No association between the exposure and the risk of developing lung cancer could be observed. CONCLUSIONS: Workers from the stone and quarry industry compensated for silicosis are at an increased risk of developing lung cancer. In order to reduce that risk, the exposure has to be lowered, with a peak exposure below 0.15 mg/m3 and an average exposure below 0.10 mg/m3.

Adult↗

Accelerated silicosis in Scottish stonemasons.

A small group of stonemasons working with sandstone was exposed to levels of respirable quartz up to 130 times the workplace standard over a period of up to 6 years. Two died of accelerated silicosis, a disease that caused serious diagnostic difficulties and was initially not recognised by the doctors of the then Department of Health and Social Security Medical Boarding Centre (respiratory diseases). Previous descriptions of this disease in the UK date back to the years of the industrial revolution (late 18th century). One other mason on the site proved to have an earlier stage of accelerated silicosis and two had radiographic changes of early classic silicosis. Regulations intended to prevent silicosis have been in place in the UK for many decades and were strengthened by the Health and Safety at Work Act in 1974. Although the workers had been aware of a health risk from quartz, they had not been able to persuade management to take effective preventive action until serious illness had occurred. Current pressures on management to cut overheads and to achieve maximum productivity could, as in this instance, lead to neglect of health and safety standards.

Adult↗

MRI signal characteristics of progressive massive fibrosis in silicosis.

AIM: To determine the magnetic resonance imaging (MRI) signal characteristics of progressive massive fibrosis (PMF) in silicosis. SUBJECTS AND METHODS: We evaluated prospectively the MR appearances in 17 patients with 34 PMF lesions on the basis of pre-contrast signal intensity (SI) and SI pattern and post-contrast enhancement pattern, using a 0.5-T unit. There were 13 PMF lesions in six patients who had silicosis and 21 PMF lesions in 11 patients who had silicotuberculosis. The SI pattern on T2-weighted image (WI) was classified into four types and the pattern of contrast enhancement on T1-WI was classified into three types. MR appearances of PMF lesions were correlated with the findings of computed tomography (CT). RESULTS: The commonest signal intensity characteristic was isointensity (70%) on T1-WI and hypointensity (68%) on T2-WI when compared with skeletal muscle. For signal pattern on T2-WI, a type with only internal high SI areas (46% in silicosis group, 38% in silicotuberculosis group) was most frequent. All of these areas corresponded to the low density areas at CT, suggestive of necrosis. After intravenous contrast medium enhancement, rim enhancement (54% in silicosis group, 52% in silicotuberculosis group) was most frequent, followed by no enhancement. CONCLUSION: The most common MRI appearance of PMF was isointensity on T1-WI and hypointensity on T2-WI when compared with skeletal muscle, with internal high SI areas on T2-WI and either rim enhancement or no enhancement.

Aged↗

Extrapulmonary silicosis: a clinical, morphologic, and ultrastructural study.

A variety of silicotic lesions derived from thoracic silicosis via lymphohematogenous spread to the liver, spleen, bone marrow, and extrathoracic lymph nodes are described. The morphologic features of these lesions depend on the extent of macrophage aggregation, the occurrence of fibrogenesis, and the development of necrosis and degradative changes in macrophages and adjacent extracellular matrix, presumably caused by lysosomal enzymes released from macrophages. Ultrastructurally, the degenerative alterations of matrix material include longitudinal splitting and breakage of collagen fibrils into segments one and three quarters the length of the original fibrils and deposition of flocculent electron-dense material either focally or diffusely around collagen fibrils. The corresponding changes viewed light microscopically are those of fibrinoid necrosis. The sclerohyaline nodule, the characteristic lesion of silicosis, includes all of these features as it evolves through nodular histiocytic and subsequent fibrohistiocytic phases. Its ultimate morphology appears to be determined by the reassembly of the degraded matrix into non-native, fibrous long-spacing collagen via a spiny collagen intermediary. The sclerohyaline nodule occurs infrequently in the spleen and liver, although less typical lesions caused by silica alone or admixed with other dusts seem to occur more commonly in these organs. These lesions appeared as loose or nodular histiocytic or fibrohistiocytic aggregates. Nonspecific fibrous nodules or more extensive fibrosis, as seen in portal triads, may represent advanced stages of such lesions. Acute or healed focal segmental glomerulonephritis occurred in 40 per cent of the cases, suggesting that it may be an important remote effect of silicosis. Continuous destruction of lymphocytes adjacent to silicotic nodules may be an antigenic source of the high concentration of autoimmune reactants described in silicosis.

Adult↗

Predictors of mortality in silicosis.

The mortality of a cohort of 1487 male patients with silicosis in a population-based register followed up from 1980 to 1986 was evaluated with reference to the mortality rates of the general male population. A striking excess of deaths from all causes (observed 368, standardized mortality ratio, SMR 3.00) was noted. Seventy-four percent of the deaths were due to respiratory conditions and complications directly or indirectly related to silicosis. The risk of death was especially higher than expected in younger patients under 45 years of age. Patients with simple silicosis of profusion category 1 did not appear to be at any increased risk of death relative to the general population, but increasing excesses of death were associated with greater extent of simple and conglomerate disease. These increased mortality risks were observed in tuberculosis-free patients as well as in those who never smoked. For the same extent of silicotic disease, the risk of death was higher if tuberculosis occurred. There was no evidence, however, that patients who smoked were more likely to suffer a worse mortality outcome than those who did not. Age at diagnosis, extent of silicotic disease and the occurrence of tuberculosis were therefore strong predictors of mortality in patients with silicosis.

Adult↗

[Silicosis or chronical obstructive bronchitis/emphysema as compensatory occupational disease].

We report on a 73-year-old man, who developed chronical bronchitis after 15 years of working as a coal miner. About 3 decades later a manifest COPD, and additionally a silicosis, were diagnosed. The silicosis was rated as an accepted case for the hazard insurance, but not as a reason for pension. The reasoning for the declining of pension for the applicant is refuted by the literature which defines occupational diseases and is generally accepted by the legislation. In this case the insurance argued that in low- to medium-grade spread of silicosis functional deficits of the lung and/or the cardio-vascular system are not to be expected. Thus the recognition and recompensation of a BK 4101 (grinders' disease, silicosis) was proposed, in contrast to the social court which demanded an expert's opinion on causality.

Aged↗

Mechanistically identified suitable biomarkers of exposure, effect, and susceptibility for silicosis and coal-worker's pneumoconiosis: a comprehensive review.

Clinical detection of silicosis is currently dependent on radiological and lung function abnormalities, both late manifestations of disease. Markers of prediction and early detection of pneumoconiosis are imperative for the implementation of timely intervention strategies. Understanding the underlying mechanisms of the etiology of coal workers pneumoconiosis (CWP) and silicosis was essential in proposing numerous biomarkers that have been evaluated to assess effects following exposure to crystalline silica and/or coal mine dust. Human validation studies have substantiated some of these proposed biomarkers and argued in favor of their use as biomarkers for crystalline silica- and CWP-induced pneumoconiosis. A number of "ideal" biological markers of effect were identified, namely, Clara cell protein-16 (CC16) (serum), tumor necrosis factor-alpha (TNF-alpha) (monocyte release), interleukin-8 (IL-8) (monocyte release), reactive oxygen species (ROS) measurement by chemiluminescence (neutrophil release), 8-isoprostanes (serum), total antioxidant levels measured by total equivalent antioxidant capacity (TEAC), glutathione, glutathione peroxidase activity, glutathione S-transferase activity, and platelet-derived growth factor (PDGF) (serum). TNF-alpha polymorphism (blood cellular DNA) was identified as a biomarker of susceptibility. Further studies are planned to test the validity and feasibility of these biomarkers to detect either high exposure to crystalline silica and early silicosis or susceptibility to silicosis in gold miners in South Africa.

Air Pollutants, Occupational↗

Historical aspects of industrial hygiene--II. Silicosis.

The extension of knowledge about silicosis, one of civilization's oldest known occupational diseases, is traced from antiquity to the twentieth century. In the past, silicosis was widely misunderstood and inadequately defined. As silicosis became widespread and concomitant with industrial and technological growth and as the numbers of workers at risk increased, new interest generated new information, and new concepts of control and prevention. Today, although we possess the significant medical and technical knowledge to prevent silicosis, there has been a failure to eradicate the disease.

History, 16th Century↗

Respiratory symptoms and pulmonary impairment in male and female subjects with pottery workers' silicosis.

Respiratory symptoms, smoking habit, lung function and radiological category of silicosis were assessed in 276 present and former pottery workers who were receiving industrial disablement benefit for silicosis. There were 140 females and 136 males. The proportion with conglomerate disease (massive fibrosis) was similar in both sexes. The FEV1 declined with increasing X-ray category of silicosis irrespective of smoking habit and was most marked in subjects with symptomatic chronic bronchitis. In females who had never smoked the average decline of FEV1 in those with simple silicosis was 18 ml year-1 and for those with conglomerate disease 38 ml year-1. Symptomatic chronic bronchitis was common and only partly related to smoking, occurring in 69% of 101 nonsmoking female silicotic patients. No significant changes were observed in vital capacity, lung volume or transfer factor for carbon monoxide.

Aged↗

Significance of genetic information in risk assessment and individual classification using silicosis as a case model.

Over the last decade the role of genetic data in epidemiological research has expanded considerably. We recently published a case-control study that evaluated the interaction between silica exposure and minor variants in the genes coding for interleukin-1alpha (IL-1alpha), interleukin-1 receptor antagonist (IL-1RA) and tumor necrosis factor alpha (TNFalpha) as risk factors associated with silicosis, a fibrotic lung disease. In contrast, this report uses data generated from these studies to illustrate the utility of genetic information for the purposes of risk assessment and clinical prediction. Specifically, this study will address how, given a known exposure, genetic information affects the characterization of risk groups. Relative operating characteristic (ROC) curves were then used to determine the impact of genetic information on individual classification. Logistic regression modeling procedures were used to estimate the predicted probability of developing silicosis. This probability was then used to construct predicted risk deciles, first for a model with occupational exposure only and then for a model containing occupational exposure and genetic main effects and interactions. Results indicate that the exposure-only model effectively captures an increasing relationship between predicted risk deciles and prevalence of observed silicosis cases. Individuals comprising the highest risk decile were almost four times as likely to have silicosis as opposed to the lowest risk decile. The addition of genetic data, however, substantially improved characterization of risk categories; the proportion of cases in the highest risk decile was almost eight times that in the lowest risk decile. However, the ROC curve and classification analysis demonstrated that the addition of genetic main effects and interactions did not significantly impact on prediction of the individual's case status. These results indicate that genetic information plays a valuable role in effectively characterizing risk groups and mechanisms of disease operating in a substantial proportion of the population. However, in the case of fibrotic lung disease caused by silica exposure, information about the presence or absence of the minor variants of IL-1alpha, IL-1RA and TNFalpha is unlikely to be a useful tool for individual classification.

Aged↗

HIV infection and silicosis: the impact of two potent risk factors on the incidence of mycobacterial disease in South African miners.

OBJECTIVE: To investigate the combined effects of HIV infection and silicosis on mycobacterial disease. DESIGN AND SETTING: A retrospective cohort of 1374 HIV-positive and 2648 HIV-negative miners who attended a South African gold mining hospital and primary health clinics. PARTICIPANTS: Miners who had been tested for HIV, with consent, at primary health clinics during 1991-1996, predominantly because of a symptomatic sexually transmitted disease. RESULTS: Tuberculosis (TB) incidence was 4.9 and 1.1 per 100 person-years in HIV-positive and HIV-negative miners respectively. The incidence of Mycobacterium kansasii disease was also high (0.32 and 0.10 per 100 person-years, respectively). Silicosis was highly prevalent, implying inadequate dust control, and was a significant TB risk factor among both HIV-positive and HIV-negative men (adjusted incidence rate ratios 1.4-2.5 according to radiological severity). The data were consistent with the risks of silicosis and HIV combining multiplicatively, but did not fit an additive model. The incidence of HIV-associated TB increased significantly during the study, with no corresponding change in HIV-negative rates, to reach 16.1 per 100 person-years among HIV-positive silicotics. CONCLUSIONS: The risks of silicosis and HIV infection combine multiplicatively, so that TB remains as much a silica-related occupational disease in HIV-positive as in HIV-negative miners, and HIV-positive silicotics have considerably higher TB incidence rates than those reported from other HIV-positive Africans. The increasing impact of HIV over time may indicate epidemic TB transmission with rapid disease development in HIV-infected miners. Similar but currently unrecognized interactions may be contributing to TB control problems in other industrializing countries affected by the HIV epidemic.

AIDS-Related Opportunistic Infections↗

Silicosis and lung cancer risk in underground uranium miners.

The presence of radiographic silicosis as a risk factor for lung cancer was assessed in a case-control study conducted within a study cohort of New Mexico underground uranium miners. Chest radiographs were interpreted for the presence of silicosis for 65 lung cancer cases and 216 controls. The presence of silicosis on the chest radiograph taken closest to the start of employment or on the latest radiograph available was not associated with lung cancer risk after adjustment for cumulative exposure to radon progeny. The odds ratio associated with the presence of any type of opacity indicative of pneumoconiosis on the chest x ray closest to the start of employment was 1.33 (95% confidence interval, 0.31-5.72). For the most recent available chest x ray, the corresponding odds ratio was 1.16 (95% confidence interval, 0.35-3.84). Although the findings are limited by the relatively small number of subjects, the lack of association of silicosis with lung cancer suggests that silica exposure should not be regarded as a major uncertainty in extrapolating radon risk estimates from miners to the general population.

Case-Control Studies↗

High-resolution CT in silicosis: correlation with radiographic findings and functional impairment.

OBJECTIVE: To assess high-resolution computed tomography (HRCT) findings in silicosis and to better define the role of HRCT in early detection of parenchymal abnormalities in silica-exposed workers. METHODS: Forty-one stone carvers were evaluated with chest radiographs (CR), HRCT, and pulmonary function tests (PFT). Inter-reader agreement was calculated using the kappa statistic (k). Correlation between radiographic and HRCT profusion scores and PFT was assessed using the Spearman correlation coefficient. RESULTS: The most common HRCT findings were branching centrilobular structures, seen in 28/41 workers (68.3%). Nodules consistent with silicosis were detected in 53.7% workers on CR and in 56.1% workers on HRCT. Inter-reader agreement for diagnosis of silicosis was better on HRCT (k = 0.84) than on CR (k = 0.54). Small opacity profusion on HRCT correlated inversely with total lung capacity and FVC%. CONCLUSION: Profusion of opacities on HRCT correlates with functional impairment. The presence of branching centrilobular structures may be helpful in early recognition of silicosis.

Adult↗

Elevated soluble Fas/APO-1 (CD95) levels in silicosis patients without clinical symptoms of autoimmune diseases or malignant tumours.

Soluble Fas (sFas) is produced as translation products of alternative mRNA splicing, and antagonizes the membranous Fas molecule in Fas/Fas ligand interactions. We investigated the serum sFas levels in 64 Japanese silicosis patients with no clinical symptoms of autoimmune diseases or malignant tumours, using ELISA for sFas. The serum sFas levels in the silicosis patients were significantly higher than those in healthy volunteers. Elevated serum sFas levels were also detected in patients with systemic lupus erythematosus but, unexpectedly, no difference was observed in sFas levels between progressive systemic sclerosis patients and healthy volunteers. On the other hand, there was no significant difference in the expression of Fas on peripheral blood lymphocytes between the patients with silicosis and age-matched healthy volunteers. These observations provided the first evidence that serum sFas levels are elevated in silicosis patients without clinical symptoms of autoimmune diseases or malignant tumours. It remains to be clarified whether patients with elevated sFas levels have a tendency to develop autoimmune diseases later, or whether some other distinct factor(s) is necessary to initiate the progression of autoimmune diseases.

Aged↗

Radiological progression and lung function in silicosis: a ten year follow up study.

Chest radiographs and spirometric tests were performed on 81 patients who had silicosis from two granite quarries in 1975, 73 of whom were followed up for two to 10 (mean 7.2) years. Each patient's initial and most recent chest radiographs were assessed independently by three experienced readers, and the yearly declines in forced expiratory volume in one second and forced vital capacity were estimated from two to four (mean 3.45) serial spirometric readings. Estimates of individual dust exposure were based on extensive historical data on hygiene. All but 11 patients were no longer exposed to dust by the start of follow up, but 24 (45%) of 53 patients who had simple silicosis and 11 (55%) of 20 who had the complicated disease showed radiological evidence of disease progression. In patients who had simple silicosis and showed no radiological progression the yearly declines in forced expiratory volume in one second and forced vital capacity were modest (64 ml/year and 59 ml/year, respectively), whereas significantly greater declines in lung function were seen in those who showed radiological evidence of progression (97 ml/year and 95 ml/year, respectively). In addition to radiological progression the previous average dust concentration to which patients had been exposed also influenced declines in both forced expiratory volume in one second and forced vital capacity after allowing for the effects of age, smoking, duration of exposure, history of tuberculosis, initial state of disease, and baseline lung function. The probability of radiological progression was most strongly influenced by the average dust concentration previously exposed to. The progression of simple silicosis is thus accompanied by appreciable declines in lung function and is strongly affected by previous levels of exposure to dust.

Dust↗

Retrospective mortality cohort study of Italian workers compensated for silicosis.

OBJECTIVES: To estimate cause specific mortality in a large cohort of Italian workers compensated for silicosis. METHODS: The cohort included 14 929 subjects (14,098 men and 831 women) compensated for silicosis between 1946 and 1979, alive on 1 January 1980, and resident in Tuscany (a region of central Italy with 3,547,000 inhabitants). Mortality follow up ranged from 1980 to 1999. Vital status and the causes of death were determined by linkage with the regional mortality registry and with the national mortality database. The cohort mortality rates were compared to the rates of the local reference population. SMRs and their 95% confidence intervals were computed assuming a Poisson distribution of the observed deaths. Specific SMR analyses were performed according to the level of disability, the year of compensation assignment, and the job type. RESULTS: A significant excess mortality was observed in male silicotics for cancer of the lung, trachea, and bronchus and cancer of the liver, respiratory diseases (silicosis, asbestosis, antracosilicosis, and other pneumoconiosis), and for tubercolosis. Statistically significant mortality excess was observed in female silicotics for respiratory diseases (specifically silicosis and other pneumoconiosis) and tuberculosis. Analyses for period of compensation assignment showed a twofold increased SMR for biliary tract cancer among female workers and for liver cancer among male workers compensated before 1970. CONCLUSIONS: The excess mortality from respiratory tract cancers and respiratory tract diseases detected in Italian compensated silicotics are in agreement with previous epidemiological studies. Although the twofold increased risk for liver cancer among males is suggestive of a possible association with silica dust exposure, the finding needs to be confirmed.

Adult↗

Mortality from non-malignant respiratory diseases among people with silicosis in Hong Kong: exposure-response analyses for exposure to silica dust.

OBJECTIVES: To examine the exposure-response relationships between various indices of exposure to silica dust and the mortality from non-malignant respiratory diseases (NMRDs) or chronic obstructive pulmonary diseases (COPDs) among a cohort of workers with silicosis in Hong Kong. METHODS: The concentrations of respirable silica dust were assigned to each industry and job task according to historical industrial hygiene measurements documented previously in Hong Kong. Exposure indices included cumulative dust exposure (CDE) and mean dust concentration (MDC). Penalised smoothing spline models were used as a preliminary step to detect outliers and guide further analyses. Multiple Cox's proportional hazard models were used to estimate the dust effects on the risk of mortality from NMRDs or COPDs after truncating the highest exposures. RESULTS: 371 of the 853 (43.49%) deaths occurring among 2789 workers with silicosis during 1981-99 were from NMRDs, and 101 (27.22%) NMRDs were COPDs. Multiple Cox's proportional hazard models showed that CDE (p = 0.009) and MDC (p<0.001) were significantly associated only with NMRD mortality. Subgroup analysis showed that deaths from NMRDs (p<0.01) and COPDs (p<0.05) were significantly associated with both CDE and MDC among underground caisson workers and among those ever employed in other occupations with high exposure to silica dust. No exposure-response relationship was observed for surface construction workers with low exposures. A clear upward trend for both NMRDs and COPDs mortality was found with increasing severity of radiological silicosis. CONCLUSION: This study documented an exposure-response relationship between exposure to silica dust and the risk of death from NMRDs or COPDs among workers with silicosis, except for surface construction workers with low exposures. The risk of mortality from NMRDs increased significantly with the progression of International Labor Organization categories, independent of dust effects.

Adult↗