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John M. Dement - One of the best experts on this subject based on the ideXlab platform.
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an epidemiological study of the role of chrysotile asbestos fibre dimensions in determining respiratory disease risk in exposed workers
Occupational and Environmental Medicine, 2008Co-Authors: Leslie Stayner, Eileen D. Kuempel, S. Gilbert, Misty J Hein, John M. DementAbstract:Background: Evidence from toxicological studies indicates that the risk of respiratory diseases varies with asbestos fibre length and width. However, there is a total lack of epidemiological evidence concerning this question. Methods: Data were obtained from a cohort mortality study of 3072 workers from an asbestos textile plant which was recently updated for vital status through 2001. A previously developed job exposure matrix based on phase contrast microscopy (PCM) was modified to provide fibre size-specific exposure estimates using data from a re-analysis of samples by transmission electron microscopy (TEM). Cox proportional hazards models were fit using alternative exposure metrics for single and multiple combinations of fibre length and diameter. Results: TEM-based cumulative exposure estimates were found to provide stronger predictions of Asbestosis and lung cancer mortality than PCM-based estimates. Cumulative exposures based on individual fibre size-specific categories were all found to be highly statistically significant predictors of lung cancer and Asbestosis. Both lung cancer and Asbestosis were most strongly associated with exposure to thin fibres ( 10 μm) fibres were found to be the strongest predictors of lung cancer, but an inconsistent pattern with fibre length was observed for Asbestosis. Cumulative exposures were highly correlated across all fibre size categories in this cohort (0.28–0.99, p values Conclusions: Asbestos fibre dimension appears to be an important determinant of respiratory disease risk. Current PCM-based methods may underestimate asbestos exposures to the thinnest fibres, which were the strongest predictor of lung cancer or Asbestosis mortality in this study. Additional studies are needed of other asbestos cohorts to further elucidate the role of fibre dimension and type.
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An epidemiological study of the role of chrysotile asbestos fibre dimensions in determining respiratory disease risk in exposed workers
Occupational and Environmental Medicine, 2008Co-Authors: Leslie Stayner, Martina Hein, Eileen D. Kuempel, S. Gilbert, John M. DementAbstract:BACKGROUND Evidence from toxicological studies indicates that the risk of respiratory diseases varies with asbestos fibre length and width. However, there is a total lack of epidemiological evidence concerning this question. METHODS Data were obtained from a cohort mortality study of 3072 workers from an asbestos textile plant which was recently updated for vital status through 2001. A previously developed job exposure matrix based on phase contrast microscopy (PCM) was modified to provide fibre size-specific exposure estimates using data from a re-analysis of samples by transmission electron microscopy (TEM). Cox proportional hazards models were fit using alternative exposure metrics for single and multiple combinations of fibre length and diameter. RESULTS TEM-based cumulative exposure estimates were found to provide stronger predictions of Asbestosis and lung cancer mortality than PCM-based estimates. Cumulative exposures based on individual fibre size-specific categories were all found to be highly statistically significant predictors of lung cancer and Asbestosis. Both lung cancer and Asbestosis were most strongly associated with exposure to thin fibres (10 microm) fibres were found to be the strongest predictors of lung cancer, but an inconsistent pattern with fibre length was observed for Asbestosis. Cumulative exposures were highly correlated across all fibre size categories in this cohort (0.28-0.99, p values
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exposure response analysis of risk of respiratory disease associated with occupational exposure to chrysotile asbestos
Occupational and Environmental Medicine, 1997Co-Authors: Leslie Stayner, John M. Dement, Randall J Smith, John Bailer, Stephen J Gilbert, Kyle Steenland, David P Brown, Richard A LemenAbstract:OBJECTIVES: To evaluate alternative models and estimate risk of mortality from lung cancer and Asbestosis after occupational exposure to chrysotile asbestos. METHODS: Data were used from a recent update of a cohort mortality study of workers in a South Carolina textile factory. Alternative exposure-response models were evaluated with Poisson regression. A model designed to evaluate evidence of a threshold response was also fitted. Lifetime risks of lung cancer and Asbestosis were estimated with an actuarial approach that accounts for competing causes of death. RESULTS: A highly significant exposure-response relation was found for both lung cancer and Asbestosis. The exposure-response relation for lung cancer seemed to be linear on a multiplicative scale, which is consistent with previous analyses of lung cancer and exposure to asbestos. In contrast, the exposure-response relation for Asbestosis seemed to be nonlinear on a multiplicative scale in this analysis. There was no significant evidence for a threshold in models of either the lung cancer or Asbestosis. The excess lifetime risk for white men exposed for 45 years at the recently revised OSHA standard of 0.1 fibre/ml was predicted to be about 5/1000 for lung cancer, and 2/1000 for Asbestosis. CONCLUSIONS: This study confirms the findings from previous investigations of a strong exposure-response relation between exposure to chrysotile asbestos and mortality from lung cancer, and Asbestosis. The risk estimates for lung cancer derived from this analysis are higher than those derived from other populations exposed to chrysotile asbestos. Possible reasons for this discrepancy are discussed.
Leslie Stayner - One of the best experts on this subject based on the ideXlab platform.
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an epidemiological study of the role of chrysotile asbestos fibre dimensions in determining respiratory disease risk in exposed workers
Occupational and Environmental Medicine, 2008Co-Authors: Leslie Stayner, Eileen D. Kuempel, S. Gilbert, Misty J Hein, John M. DementAbstract:Background: Evidence from toxicological studies indicates that the risk of respiratory diseases varies with asbestos fibre length and width. However, there is a total lack of epidemiological evidence concerning this question. Methods: Data were obtained from a cohort mortality study of 3072 workers from an asbestos textile plant which was recently updated for vital status through 2001. A previously developed job exposure matrix based on phase contrast microscopy (PCM) was modified to provide fibre size-specific exposure estimates using data from a re-analysis of samples by transmission electron microscopy (TEM). Cox proportional hazards models were fit using alternative exposure metrics for single and multiple combinations of fibre length and diameter. Results: TEM-based cumulative exposure estimates were found to provide stronger predictions of Asbestosis and lung cancer mortality than PCM-based estimates. Cumulative exposures based on individual fibre size-specific categories were all found to be highly statistically significant predictors of lung cancer and Asbestosis. Both lung cancer and Asbestosis were most strongly associated with exposure to thin fibres ( 10 μm) fibres were found to be the strongest predictors of lung cancer, but an inconsistent pattern with fibre length was observed for Asbestosis. Cumulative exposures were highly correlated across all fibre size categories in this cohort (0.28–0.99, p values Conclusions: Asbestos fibre dimension appears to be an important determinant of respiratory disease risk. Current PCM-based methods may underestimate asbestos exposures to the thinnest fibres, which were the strongest predictor of lung cancer or Asbestosis mortality in this study. Additional studies are needed of other asbestos cohorts to further elucidate the role of fibre dimension and type.
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An epidemiological study of the role of chrysotile asbestos fibre dimensions in determining respiratory disease risk in exposed workers
Occupational and Environmental Medicine, 2008Co-Authors: Leslie Stayner, Martina Hein, Eileen D. Kuempel, S. Gilbert, John M. DementAbstract:BACKGROUND Evidence from toxicological studies indicates that the risk of respiratory diseases varies with asbestos fibre length and width. However, there is a total lack of epidemiological evidence concerning this question. METHODS Data were obtained from a cohort mortality study of 3072 workers from an asbestos textile plant which was recently updated for vital status through 2001. A previously developed job exposure matrix based on phase contrast microscopy (PCM) was modified to provide fibre size-specific exposure estimates using data from a re-analysis of samples by transmission electron microscopy (TEM). Cox proportional hazards models were fit using alternative exposure metrics for single and multiple combinations of fibre length and diameter. RESULTS TEM-based cumulative exposure estimates were found to provide stronger predictions of Asbestosis and lung cancer mortality than PCM-based estimates. Cumulative exposures based on individual fibre size-specific categories were all found to be highly statistically significant predictors of lung cancer and Asbestosis. Both lung cancer and Asbestosis were most strongly associated with exposure to thin fibres (10 microm) fibres were found to be the strongest predictors of lung cancer, but an inconsistent pattern with fibre length was observed for Asbestosis. Cumulative exposures were highly correlated across all fibre size categories in this cohort (0.28-0.99, p values
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exposure response analysis of risk of respiratory disease associated with occupational exposure to chrysotile asbestos
Occupational and Environmental Medicine, 1997Co-Authors: Leslie Stayner, John M. Dement, Randall J Smith, John Bailer, Stephen J Gilbert, Kyle Steenland, David P Brown, Richard A LemenAbstract:OBJECTIVES: To evaluate alternative models and estimate risk of mortality from lung cancer and Asbestosis after occupational exposure to chrysotile asbestos. METHODS: Data were used from a recent update of a cohort mortality study of workers in a South Carolina textile factory. Alternative exposure-response models were evaluated with Poisson regression. A model designed to evaluate evidence of a threshold response was also fitted. Lifetime risks of lung cancer and Asbestosis were estimated with an actuarial approach that accounts for competing causes of death. RESULTS: A highly significant exposure-response relation was found for both lung cancer and Asbestosis. The exposure-response relation for lung cancer seemed to be linear on a multiplicative scale, which is consistent with previous analyses of lung cancer and exposure to asbestos. In contrast, the exposure-response relation for Asbestosis seemed to be nonlinear on a multiplicative scale in this analysis. There was no significant evidence for a threshold in models of either the lung cancer or Asbestosis. The excess lifetime risk for white men exposed for 45 years at the recently revised OSHA standard of 0.1 fibre/ml was predicted to be about 5/1000 for lung cancer, and 2/1000 for Asbestosis. CONCLUSIONS: This study confirms the findings from previous investigations of a strong exposure-response relation between exposure to chrysotile asbestos and mortality from lung cancer, and Asbestosis. The risk estimates for lung cancer derived from this analysis are higher than those derived from other populations exposed to chrysotile asbestos. Possible reasons for this discrepancy are discussed.
A W Musk - One of the best experts on this subject based on the ideXlab platform.
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the effect of Asbestosis on lung cancer risk beyond the dose related effect of asbestos alone
Occupational and Environmental Medicine, 2005Co-Authors: Alison Reid, Gina L Ambrosini, Nola Olsen, N H De Klerk, S C Pang, G Berry, A W MuskAbstract:Aims: To determine if the presence of Asbestosis is a prerequisite for lung cancer in subjects with known exposure to blue asbestos (crocidolite). Methods: Former workers and residents of Wittenoom with known amounts of asbestos exposure (duration, intensity, and time since first exposure), current chest x ray and smoking information, participating in a cancer prevention programme (n = 1988) were studied. The first plain chest radiograph taken at the time of recruitment into the cancer prevention programme was examined for radiographic evidence of Asbestosis according to the UICC (ILO) classification. Cox proportional hazards modelling was used to relate Asbestosis, asbestos exposure, and lung cancer. Results: Between 1990 and 2002 there were 58 cases of lung cancer. Thirty six per cent of cases had radiographic evidence of Asbestosis compared to 12% of study participants. Smoking status was the strongest predictor of lung cancer, with current smokers (OR = 26.5, 95% CI 3.5 to 198) having the greatest risk. Radiographic Asbestosis (OR = 1.94, 95% CI 1.09 to 3.46) and asbestos exposure (OR = 1.21 per f/ml-year, 95% CI 1.02 to 1.42) were significantly associated with an increased risk of lung cancer. There was an increased risk of lung cancer with increasing exposure in those without Asbestosis. Conclusion: In this cohort of former workers and residents of Wittenoom, Asbestosis is not a mandatory precursor for asbestos related lung cancer. These findings support the hypothesis that it is the asbestos fibres per se that cause lung cancer, which can develop with or without the presence of Asbestosis.
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the additional risk of malignant mesothelioma in former workers and residents of wittenoom with benign pleural disease or Asbestosis
Occupational and Environmental Medicine, 2005Co-Authors: Alison Reid, Gina L Ambrosini, Nola Olsen, N H De Klerk, S C Pang, A W MuskAbstract:Aims: To examine the hypothesis that people with benign pleural disease or Asbestosis have an increased risk of malignant mesothelioma beyond that attributable to their degree of asbestos exposure. Methods: Former workers and residents of the crocidolite mining and milling town of Wittenoom are participating in a cancer prevention programme (n = 1988). The first plain chest radiograph taken at the time of recruitment into the cancer prevention programme was read for evidence of benign pleural disease and Asbestosis, using the UICC classification. Crocidolite exposure of former workers was derived from employment records and records of dust measurements performed during the operation of the asbestos mine and mill between 1943 and 1966. Based on fibre counts, exposure for former residents was determined using duration of residence and period of residence (before and after a new mill was commissioned in 1957) and interpolation from periodic hygienic measures undertaken from personal monitors between 1966 and 1992. Cox proportional hazards modelling was used to relate benign pleural disease, Asbestosis, asbestos exposure, and mesothelioma. Results: Between 1990 and 2002, there were 76 cases of mesothelioma (56 of the pleura and 20 of the peritoneum). Cases had more radiographic evidence of (all) benign pleural disease, pleural thickening, blunt/obliterated costophrenic angle, and Asbestosis than non-cases. Adjusting for time since first exposure (log years), cumulative exposure (log f/ml-years), and age at the start of the programme, pleural thickening (OR = 3.1, 95% CI 1.2 to 7.6) and Asbestosis (OR = 3.3, 95% CI 1.3 to 8.6) were associated with an increased risk of peritoneal mesothelioma. There was no increased risk for pleural mesothelioma. Conclusion: The presence of benign pleural disease, in particular pleural thickening, and Asbestosis appears to increase the risk of mesothelioma of the peritoneum, but not of the pleura beyond that attributable to indices of asbestos exposure in this cohort of subjects exposed to crocidolite.
Panu Oksa - One of the best experts on this subject based on the ideXlab platform.
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Proteomic detection of cancer in Asbestosis patients using SELDI-TOF discovered serum protein biomarkers
Biomarkers, 2011Co-Authors: Brian C. Tooker, Lee S. Newman, Antti Karjalainen, Panu Oksa, Harri Vainio, Eero Pukkala, Russell P Bowler, Paul W. Brandt-raufAbstract:Objectives: To identify biomarkers for cancer in Asbestosis patients.Methods: SELDI-TOF and CART were used to identify serum biomarker profiles in 35 Asbestosis patients who subsequently developed cancer and 35 did not develop cancer.Results: Three polypeptide peaks (5707.01, 6598.10, and 20,780.70 Da) could predict the development of cancer with 87% sensitivity and 70% specificity. The first two peaks were identified as KIF18A and KIF5A, respectively, and are part of the Kinesin Superfamily of proteins.Conclusions: We identified two Kinesin proteins that can be potentially used as blood biomarkers to identify Asbestosis patients at risk of developing lung cancer.
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increased alveolar nitric oxide concentration and high levels of leukotriene b4 and 8 isoprostane in exhaled breath condensate in patients with Asbestosis
Thorax, 2007Co-Authors: Hannele Lehtonen, Panu Oksa, Lauri Lehtimaki, Anna Sepponen, Riina Nieminen, Hannu Kankaanranta, Seppo Saarelainen, Ritva Jarvenpaa, Jukka Uitti, Eeva MoilanenAbstract:Background: Inhaled asbestos fibres can cause inflammation and fibrosis in the lungs called Asbestosis. However, there are no non-invasive means to assess and follow the severity of the inflammation. Exhaled nitric oxide (NO) measured at multiple exhalation flow rates can be used to assess the alveolar NO concentration and bronchial NO flux, which reflect inflammation in the lung parenchyma and airways, respectively. The aim of the present study was to investigate whether exhaled NO or markers in exhaled breath condensate could be used to assess inflammation in Asbestosis. Methods: Exhaled NO and inflammatory markers (leukotriene B4 and 8-isoprostane) in exhaled breath condensate were measured in 15 non-smoking patients with Asbestosis and in 15 healthy controls. Exhaled NO concentrations were measured at four constant exhalation flow rates (50, 100, 200 and 300 ml/s) and alveolar NO concentration and bronchial NO flux were calculated according to the linear model of pulmonary NO dynamics. Results: The mean (SE) alveolar NO concentration was significantly higher in patients with Asbestosis than in controls (3.2 (0.4) vs 2.0 (0.2) ppb, p = 0.008). There was no difference in bronchial NO flux (0.9 (0.1) vs 0.9 (0.1) nl/s, p = 0.93) or NO concentration measured at ATS standard flow rate of 50 ml/s (20.0 (2.0) vs 19.7 (1.8) ppb, p = 0.89). Patients with Asbestosis had increased levels of leukotriene B4 (39.5 (6.0) vs 15.4 (2.9) pg/ml, p = 0.002) and 8-isoprostane (33.5 (9.6) vs 11.9 (2.8) pg/ml, p = 0.048) in exhaled breath condensate and raised serum levels of C-reactive protein (2.3 (0.3) vs 1.1 (0.2) μg/ml, p = 0.003), interleukin-6 (3.5 (0.5) vs 1.7 (0.4) pg/ml, p = 0.007) and myeloperoxidase (356 (48) vs 240 (20) ng/ml, p = 0.034) compared with healthy controls. Conclusions: Patients with Asbestosis have an increased alveolar NO concentration and high levels of leukotriene B4 and 8-isoprostane in exhaled breath. Measurement of exhaled NO at multiple exhalation flow rates and analysis of inflammatory markers in exhaled breath condensate are promising non-invasive means for assessing inflammation in patients with Asbestosis.
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progression of Asbestosis predicts lung cancer
Chest, 1998Co-Authors: Panu Oksa, Antti Karjalainen, Eero Pukkala, Matti S. Huuskonen, Matti Klockars, Kimmo Vattulainen, Henrik NordmanAbstract:Study objectives To explore whether the progression of Asbestosis correlates with the risk of lung cancer among patients with Asbestosis. Design A group of 85 Asbestosis patients (78 men and 7 women) were radiographically followed up between 1979 and 1987. Two or three posteroanterior radiographs taken from each patient in 1978 to 1979, 1983 to 1984, and 1986 to 1987 were classified according to the International Labour Office 1980 classification and were used to divide the patients into progressors and nonprogressors. Follow-up for cancer was done automatically through the files of the Finnish Cancer Registry from the time of determination of the progression status to December 31, 1994. Predictors of lung cancer risk were studied with a logistic regression model, and the standardized incidence ratio (SIR) was calculated for lung cancer. Results Of the 24 male patients with progressive small opacity profusion, 11 (46%) developed lung cancer, as opposed to 5 (9%) of the 54 male patients without progression. The SIR for lung cancer was 37 (95% confidence interval, 18 to 66) for the progressors and 4.3 (1.4 to 9.9) for the nonprogressors. In both groups, all the lung cancer cases occurred among smokers or exsmokers. None of the seven female patients showed progressive small opacity profusion. One of them developed lung cancer. In the logistic regression model including all 85 Asbestosis patients, radiographic progression of small opacity profusion (p=0.0009) and current smoking (0.0021) were significant predictors of lung cancer morbidity. Conclusions Asbestosis patients with radiographic progression of small opacity profusion over a few years are at a higher risk of lung cancer than those with a less aggressive course of the disease. The progression of pulmonary fibrosis may be an independent risk factor that, in addition to smoking history and the intensity of asbestos exposure, could be used to estimate lung cancer risk.
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Neurological signs in relation to cancer in patients with Asbestosis.
Occupational and Environmental Medicine, 1997Co-Authors: J. Juntunen, Panu Oksa, Eero Pukkala, Pekka LaippalaAbstract:OBJECTIVE: To chart the subtle neurological abnormalities in patients with Asbestosis relative to possible development of cancer. METHODS: In 1979-81 a standardised neurological examination was made of 115 patients with Asbestosis who carried a high risk of occupational cancer and their cancer morbidity was analysed 15 years later. RESULTS: Slight disturbances of unknown aetiology were found in the central nervous system (CNS) of 33 and in the peripheral nervous system (PNS) of 41 patients. Of these 17 had disturbances of both the CNS and PNS. This cohort was followed up to the end of 1994. During this time 47 of the patients developed cancer. Statistical analyses showed that disturbances of the CNS such as psycho-organic syndrome, cerebellar dysfunction, and motor disturbances of unknown origin were significantly associated with cancer, whereas no such association was found for peripheral neuropathy. Interaction between the radiological progression of Asbestosis and disturbances of the CNS was an even stronger predictor of cancer. CONCLUSIONS: It seems that slight disturbances of the CNS are predictors of development of cancer. Whether or not these disturbances are manifestations of involvement of a paraneoplastic nervous system or some factor associated with progression of Asbestosis remains open.
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serum oncoproteins in Asbestosis patients
Clinical Chemistry, 1995Co-Authors: Riitta Partanen, Panu Oksa, Heikki Koskinen, Karl Hemminki, Walter Carney, Steven Smith, Paul BrandtraufAbstract:Using ELISAs, we determined the concentrations of transforming growth factor alpha (TGF-alpha), the extracellular domain of the erbB-2 receptor (erbB-2 ECD), and mutant p53 protein in stored serum samples of Asbestosis patients with and without cancer and control subjects (without Asbestosis or cancer). The percentage of individuals in these three groups with increased serum concentrations of TGF-alpha, erbB-2 ECD, and mutant p53, respectively, were: Asbestosis patients with cancer, 36%, 16%, 19%; Asbestosis patients without cancer, 38%, 19%, 6%; control subjects, 0%, 5%, 10%. Although differences in serum positivity for these oncoproteins were apparent among these groups, the differences did not achieve statistical significance (P > 0.05). In several of the cancer cases, increased concentrations of TGF-alpha, erbB-2 ECD, and mutant p53 were also detected in the stored serum samples collected years before the clinical diagnosis of disease.
Eileen D. Kuempel - One of the best experts on this subject based on the ideXlab platform.
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an epidemiological study of the role of chrysotile asbestos fibre dimensions in determining respiratory disease risk in exposed workers
Occupational and Environmental Medicine, 2008Co-Authors: Leslie Stayner, Eileen D. Kuempel, S. Gilbert, Misty J Hein, John M. DementAbstract:Background: Evidence from toxicological studies indicates that the risk of respiratory diseases varies with asbestos fibre length and width. However, there is a total lack of epidemiological evidence concerning this question. Methods: Data were obtained from a cohort mortality study of 3072 workers from an asbestos textile plant which was recently updated for vital status through 2001. A previously developed job exposure matrix based on phase contrast microscopy (PCM) was modified to provide fibre size-specific exposure estimates using data from a re-analysis of samples by transmission electron microscopy (TEM). Cox proportional hazards models were fit using alternative exposure metrics for single and multiple combinations of fibre length and diameter. Results: TEM-based cumulative exposure estimates were found to provide stronger predictions of Asbestosis and lung cancer mortality than PCM-based estimates. Cumulative exposures based on individual fibre size-specific categories were all found to be highly statistically significant predictors of lung cancer and Asbestosis. Both lung cancer and Asbestosis were most strongly associated with exposure to thin fibres ( 10 μm) fibres were found to be the strongest predictors of lung cancer, but an inconsistent pattern with fibre length was observed for Asbestosis. Cumulative exposures were highly correlated across all fibre size categories in this cohort (0.28–0.99, p values Conclusions: Asbestos fibre dimension appears to be an important determinant of respiratory disease risk. Current PCM-based methods may underestimate asbestos exposures to the thinnest fibres, which were the strongest predictor of lung cancer or Asbestosis mortality in this study. Additional studies are needed of other asbestos cohorts to further elucidate the role of fibre dimension and type.
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An epidemiological study of the role of chrysotile asbestos fibre dimensions in determining respiratory disease risk in exposed workers
Occupational and Environmental Medicine, 2008Co-Authors: Leslie Stayner, Martina Hein, Eileen D. Kuempel, S. Gilbert, John M. DementAbstract:BACKGROUND Evidence from toxicological studies indicates that the risk of respiratory diseases varies with asbestos fibre length and width. However, there is a total lack of epidemiological evidence concerning this question. METHODS Data were obtained from a cohort mortality study of 3072 workers from an asbestos textile plant which was recently updated for vital status through 2001. A previously developed job exposure matrix based on phase contrast microscopy (PCM) was modified to provide fibre size-specific exposure estimates using data from a re-analysis of samples by transmission electron microscopy (TEM). Cox proportional hazards models were fit using alternative exposure metrics for single and multiple combinations of fibre length and diameter. RESULTS TEM-based cumulative exposure estimates were found to provide stronger predictions of Asbestosis and lung cancer mortality than PCM-based estimates. Cumulative exposures based on individual fibre size-specific categories were all found to be highly statistically significant predictors of lung cancer and Asbestosis. Both lung cancer and Asbestosis were most strongly associated with exposure to thin fibres (10 microm) fibres were found to be the strongest predictors of lung cancer, but an inconsistent pattern with fibre length was observed for Asbestosis. Cumulative exposures were highly correlated across all fibre size categories in this cohort (0.28-0.99, p values
