Cohort mortality study of North American industrial sand workers. II. Case-referent analysis of lung cancer and silicosis deaths.
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BACKGROUND: A cohort mortality study of 2670 men in nine North American industrial sand plants resulted in 83 deaths from lung cancer 20 or more years after hire (standardized mortality ratio 139) and 37 deaths from silicosis (including seven from silico-tuberculosis). The lung cancer excess was unrelated to duration of employment and not found in all plants. OBJECTIVES: The primary aim was to determine whether lung cancer risk among these employees was related to quantitative estimates of crystalline silica exposure, after allowance for cigarette smoking. A secondary aim was to do the same for silicosis mortality, partly as a means of validating the estimated levels of exposure. METHODS: A nested case-referent study was undertaken with cases matched with up to two controls on plant, age and date of first employment from men who survived the case. Exposures were estimated by linking work histories to a job-exposure matrix, undertaken separately. Cigarette smoking information was obtained from medical records and other sources, blind as to case-control status. Matched statistical analyses were conducted using conditional logistic regression. FINDINGS: Odds ratios for silicosis mortality were significantly related to cumulative silica exposures and tended to a relationship with category of average crystalline silica concentration, but inconsistently with length of employment. After accounting for a strong effect of cigarette smoking, odds ratios for lung cancer were related to cumulative crystalline silica exposure and to average silica concentration, but not to length of employment. CONCLUSION: These findings support a causal relationship between lung cancer and quartz exposure after allowance for cigarette smoking, in the absence of cristobalite or other known occupational carcinogens. (+info)
A patient with asbestos-induced lung cancer complicated by silicosis.
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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. (+info)
Radiological progression and its predictive risk factors in silicosis.
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OBJECTIVES: To investigate the risk factors predicting radiological progression in silicosis in a prospective cohort study of patients with silicosis who were previously exposed to silica from granite dust. METHODS: From among a total of 260 patients with silicosis contracted from granite work, 141 with available serial chest x ray films of acceptable quality taken over a period of 2 to 17 (mean 7.5) years, were selected for study. Ninety four (66.7%) had ended exposure 5 or more years previously (mean 10.1 years, maximum 28 years). Radiological progression was assessed by paired comparison of the initial and most recent radiographs, with two or more steps of increase in profusion of small opacities according to the 12 point scale of the International Labour Organisation (ILO) classification of radiographs of pneumoconiosis, taken from the majority reading by a panel of three independent readers. RESULTS: Overall, 37% of patients with silicosis had radiological evidence of progression. From the initial radiographs, 24 (31.6%) of those with radiological profusion category 1, 15 (37.5%) of those with radiological profusion category 2, and 13 (52%) of those with complicated silicosis (including all seven with category 3 profusion of small opacities) showed radiological progression. As expected, progression was more likely to be found after longer periods of follow up (the interval between the two chest x ray films) with a 20% increased odds of progression for every additional year of follow up. After adjustment for varying intervals of follow up, the probability of radiological progression was found to be significant if large opacities were present in the initial chest x ray film. Progression was also less likely to be found among those who had ended exposure to silica longer ago, although the result was of borderline significance (p=0.07). Tuberculosis was also associated with increased likelihood of progression (borderline significance). CONCLUSIONS: There is a high probability of radiological progression in silicosis after high levels of exposure to granite dust among workers who were followed up for up to 17 years. A significant risk factor is the extent of radiological opacities in the initial chest x ray film. The probability of progression is also likely to be reduced with longer periods after the end of exposure. (+info)
Polymorphisms in the IkappaB-alpha promoter region and risk of diseases involving inflammation and fibrosis.
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The transcription factor NFkappaB regulates inflammatory and other cellular responses. In non-stimulated cells, NFkappaB is linked to its inhibitor IkappaB, which plays a major role in controlling NFkappaB activity. Here, the gene promoter region of the major inducible IkappaB component (IkappaB-alpha) was studied to identify single nucleotide polymorphisms (SNPs), and to test if these are associated with risk of two diseases involving inflammation and fibrosis (trachoma and silicosis). Three SNPs were identified at positions -881, -826 and -297 relative to the transcription start site. The position -297 is close to two NFkappaB binding sites, kappaB2 and kappaB3, but the alleles were not associated with either disease. Alleles at positions -881 and -826 were in complete linkage disequilibrium with each other, and the rare haplotype was significantly less frequent among patients with trachoma compared to controls, although there was no difference in frequencies between silicosis patients and controls. (+info)
Fas ligand triggers pulmonary silicosis.
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We investigated the role of Fas ligand in murine silicosis. Wild-type mice instilled with silica developed severe pulmonary inflammation, with local production of tumor necrosis factor (TNF)-alpha, and interstitial neutrophil and macrophage infiltration in the lungs. Strikingly, Fas ligand-deficient generalized lymphoproliferative disease mutant (gld) mice did not develop silicosis. The gld mice had markedly reduced neutrophil extravasation into bronchoalveolar space, and did not show increased TNF-alpha production, nor pulmonary inflammation. Bone marrow chimeras and local adoptive transfer demonstrated that wild-type, but not Fas ligand-deficient lung macrophages recruit neutrophils and initiate silicosis. Silica induced Fas ligand expression in lung macrophages in vitro and in vivo, and promoted Fas ligand-dependent macrophage apoptosis. Administration of neutralizing anti-Fas ligand antibody in vivo blocked induction of silicosis. Thus, Fas ligand plays a central role in induction of pulmonary silicosis. (+info)
Cumulative exposure to dust causes accelerated decline in lung function in tunnel workers.
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OBJECTIVES: To examine whether underground construction workers exposed to tunnelling pollutants over a follow up period of 8 years have an increased risk of decline in lung function and respiratory symptoms compared with reference subjects working outside the tunnel atmosphere, and relate the findings to job groups and cumulative exposure to dust and gases. METHODS: 96 Tunnel workers and a reference group of 249 other heavy construction workers were examined in 1991 and re-examined in 1999. Exposure measurements were carried out to estimate personal cumulative exposure to total dust, respirable dust, alpha-quartz, oil mist, and nitrogen dioxide. The subjects answered a questionnaire on respiratory symptoms and smoking habits, performed spirometry, and had chest radiographs taken. Radiological signs of silicosis were evaluated (International Labour Organisation (ILO) classification). Atopy was determined by a multiple radioallergosorbent test (RAST). RESULTS: The mean exposure to respirable dust and alpha-quartz in tunnel workers varied from 1.2-3.6 mg/m3 (respirable dust) and 0.019-0.044 mg/m3 (alpha-quartz) depending on job task performed. Decrease in forced expiratory volume in 1 second (FEV1) was associated with cumulative exposure to respirable dust (p<0.001) and alpha-quartz (p=0.02). The multiple regression model predicted that in a worker 40 years of age, the annual decrease in FEV1 would be 25 ml in a non-exposed non-smoker, 35 ml in a non-exposed smoker, and 50-63 ml in a non-smoking tunnel worker (depending on job). Compared with the reference group the odds ratio for the occurrence of new respiratory symptoms during the follow up period was increased in the tunnel workers and associated with cumulative exposure to respirable dust. CONCLUSIONS: Cumulative exposures to respirable dust and alpha-quartz are the most important risk factors for airflow limitation in underground heavy construction workers, and cumulative exposure to respirable dust is the most important risk factor for respiratory symptoms. The finding of accelerated decline in lung function in tunnel workers suggests that better control of exposures is needed. (+info)
Mortality from lung cancer among silicotic patients in Sardinia: an update study with 10 more years of follow up.
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OBJECTIVES: To evaluate the association between silica, silicosis and lung cancer, the mortality of 724 patients with silicosis, first diagnosed by standard chest x ray film between 1964 and 1970, has been analysed by a cohort study extended to 31 December 1997. METHODS: Smoking and detailed occupational histories were available for each member of the cohort as well as the estimated lifetime exposure to respirable silica dust and radon daughters. Two independent readers blindly classified standard radiographs according to the 12 point International Labour Organisation (ILO) scale. Lung function tests meeting the American Thoracic Society's criteria were available for 665 patients. Standardised mortality ratios (SMRs) for selected causes of death were based on the age specific Sardinian regional death rates. RESULTS: The mortality for all causes was significantly higher than expected (SMR 1.35, 95% confidence interval (95% CI) 1.24 to 1.46) mainly due to tuberculosis (SMR 22.0) and to non-malignant chronic respiratory diseases (NMCRD) (SMR 6.03). All cancer deaths were within the expected numbers (SMR 0.93; 95% CI 0.76 to 1.14). The SMR for lung cancer was 1.37 (95% CI 0.98 to 1.91, 34 observed), increasing to 1.65 (95% CI 0.98 to 2.77) allowing for 20 years of latency since the first diagnosis of silicosis. Although mortality from NMCRD was strongly associated to the severity of radiological silicosis and to the extent of the cumulative exposure to silica, SMR for lung cancer was weakly related to the ILO categories and to the cumulative exposure to silica dust only after 20 years of lag interval. A significant excess of deaths from lung cancer (SMR 2.35) was found among silicotic patients previously employed in underground metal mines characterised by a relatively high airborne concentration of radon daughters and among ever smokers who showed an airflow obstruction at the time of the first diagnosis of silicosis (SMR 3.29). Mortality for lung cancer related to exposure was evaluated with both the Cox's proportional hazards modelling within the entire cohort and a nested case-control study (34 cases of lung cancer and 136 matched controls). Both multivariate analyses did not show any significant association with cumulative exposure to silica or severity of silicosis, but confirmed the association between mortality for lung cancer and relatively high exposure to radon, smoking, and airflow obstruction as significant covariates. CONCLUSIONS: The findings indicate that the slightly increased mortality for lung cancer in this cohort of silicotic patients was significantly associated with other risk factors-such as cigarette smoking, airflow obstruction, and estimated exposure to radon daughters in underground mines-rather than to the severity of radiological silicosis or to the cumulative exposure to crystalline silica dust itself. (+info)
Lymphopenia in occupational pulmonary silicosis with or without autoimmune disease.
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An increased prevalence of autoimmune diseases such as rheumatoid arthritis has been demonstrated in silica-exposed patients. The aim of this study was to determine the peripheral blood lymphocyte phenotype in a population of silicotic workers employed in the slate mines of the district. Silicosis was assessed in 58 patients according to the International Labor Office's criteria. Clinical and biological data including flow cytometric evaluation of the lymphocyte subsets were compared with those from 41 healthy volunteers. The silicotic patients had a higher prevalence of autoimmune diseases (6/58 versus 0/41: P < 0.05) and of elevated antinuclear antibody titres compared to the control group. A very significant decrease of total lymphocyte count (P < 0.001) involving B, T and Natural Killer cells was found in silicotic patients as compared with matched healthy volunteers. A significant increase in the percentage of activated T cells (12.3%) was observed in the silicotic group as compared to 6.5% in the control group (P = 5 x 10(-5)). Our results show that in silicotic patients, the absolute number of circulating lymphocytes is diminished with an increased proportion of activated T cells. Whether these findings could predispose to the development of autoimmune disorders is discussed. (+info)