Follow-up of Soluble Mesothelin-Related Protein Levels in Participants With Asbestos-Related Disorders.

BACKGROUND: Asbestos exposure is associated with the development of the cancer malignant mesothelioma (MM). Measurement of soluble mesothelin-related protein (SMRP) has been suggested as a method for detection of MM in its early stages. We prospectively examined SMRP levels in participants with asbestos exposure who are a group at a high risk of development of MM. METHODS: This study was a follow-up of our cohort of 322 asbestos-exposed participants. No further participants developed MM or malignancy over the study period. Mean follow-up time was 22.9 months. RESULTS: Mean (standard deviation) SMRP levels at baseline and follow-up were 0.94 (0.79) and 0.91 (0.86) nmol/L (p = 0.1033), respectively. Mean SMRP levels of the healthy individuals exposed to asbestos at baseline was significantly lower than those of participants with asbestosis and pleural plaques alone; similar patterns were found on follow-up measurements. There was a statistically significant effect of age on serial SMRP measurements. Our study confirms higher levels in participants with nonmalignant asbestos-related disorders. Levels decreased in asbestos-related disorders other than asbestosis, where a small increase was observed. We did not detect any further cases of malignancy. CONCLUSION: Monitoring programs for early detection of MM need to take into account increased SMRP levels found in benign asbestos-related diseases.

Respiratory surveillance for coal mine dust and artificial stone exposed workers in Australia and New Zealand: A position statement from the Thoracic Society of Australia and New Zealand.

Coal mine lung dust disease (CMDLD) and artificial stone (AS) silicosis are preventable diseases which have occurred in serious outbreaks in Australia recently. This has prompted a TSANZ review of Australia's approach to respiratory periodic health surveillance. While regulating respirable dust exposure remains the foundation of primary and secondary prevention, identification of workers with early disease assists with control of further exposure, and with the aims of preserving lung function and decreasing respiratory morbidity in those affected. Prompt detection of an abnormality also allows for ongoing respiratory specialist clinical management. This review outlines a medical framework for improvements in respiratory surveillance to detect CMDLD and AS silicosis in Australia. This includes appropriate referral, improved data collection and interpretation, enhanced surveillance, the establishment of a nationwide Occupational Lung Disease Registry and an independent advisory group. These measures are designed to improve health outcomes for workers in the coal mining, AS and other dust-exposed and mining industries.

Artificial stone-associated silicosis: a rapidly emerging occupational lung disease.

INTRODUCTION: Artificial stone is an increasingly popular material used to fabricate kitchen and bathroom benchtops. Cutting and grinding artificial stone is associated with generation of very high levels of respirable crystalline silica, and the frequency of cases of severe silicosis associated with this exposure is rapidly increasing. AIM: To report the characteristics of a clinical series of Australian workers with artificial stone-associated silicosis. METHODS: Respiratory physicians voluntarily reported cases of artificial stone-associated silicosis identified in their clinical practices. Physicians provided information including occupational histories, respiratory function tests, chest radiology and histopathology reports, when available. RESULTS: Seven male patients were identified with a median age of 44 years (range 26-61). All were employed in small kitchen and bathroom benchtop fabrication businesses with an average of eight employees (range 2-20). All workplaces primarily used artificial stone, and dust control measures were poor. All patients were involved in dry cutting artificial stone. The median duration of exposure prior to symptoms was 7 years (range 4-10). Six patients demonstrated radiological features of progressive massive fibrosis. These individuals followed up over a median follow-up period of 16 months (IQR 21 months) demonstrated rapid decline in prebronchodilator forced expiratory volume in 1 s of 386 mL/year (SD 204 mL) and forced vital capacity of 448 mL/year (SD 312 mL). CONCLUSIONS: This series of silicosis in Australian workers further demonstrates the risk-associated high-silica content artificial stone. Effective dust control and health surveillance measures need to be stringently implemented and enforced in this industry.

Coal workers' pneumoconiosis: an Australian perspective.

Coal workers' pneumoconiosis (CWP) is an untreatable but preventable lung disease arising from chronic inhalation of coal dust. Recent reports of CWP in Queensland, along with international data, suggest that there is a resurgence in pneumoconiosis. The prevalence of CWP varies considerably between countries. In Australia, there is no mandatory reporting system and no national data on the prevalence of CWP. The symptoms and manifestations of CWP vary depending on the composition of the inhaled dust, duration of exposure, stage of disease and host-related factors. CWP may develop into progressive massive fibrosis (PMF), which can be fatal. Radiological assessment should be performed according to evidence-based standards using the ILO (International Labour Office) International Classification of Radiographs of Pneumoconioses. As preventing exposure to coal dust prevents CWP, it is important to implement and enforce appropriate standards limiting exposure. In Australia, these standards currently vary between states and are not in keeping with international understanding of the levels of coal dust that cause disease. Longitudinal screening programs are crucial for monitoring the health of coal workers to identify individuals with early-stage disease and prevent progression from mild disease to PMF. We recommend: standardisation of coal dust exposure limits, with harmonisation to international regulations; implementation of a national screening program for at-risk workers, with use of standardised questionnaires, imaging and lung function testing; development of appropriate training materials to assist general practitioners in identifying pneumoconiosis; and a system of mandatory reporting of CWP to a centralised occupational lung disease register.

Asbestos exposure during home renovation in New South Wales.

OBJECTIVE: Asbestos exposure is causally associated with the development of malignant mesothelioma (MM), which is increasingly being reported after exposure to asbestos fibro sheeting in Australia. In this study, we investigate self-reported non-occupational asbestos exposure during home renovation in New South Wales. DESIGN AND SETTING: Cross-sectional mailed questionnaire examining renovation activity, tasks undertaken during renovation and self-reported exposure to asbestos among respondents and their family members in NSW between January and June 2008. PARTICIPANTS: 10 000 adults aged 18-99 years, randomly selected from the NSW electoral roll. We received 3612 responses, while 365 questionnaires did not reach addressees, giving an overall response rate of 37.5%. MAIN OUTCOME MEASURES: Differences in self-reported asbestos exposure between do-it-yourself (DIY) and non-DIY renovators. RESULTS: 1597 participants (44.2%) had renovated their home and among these, 858 participants (53.7%) self-reported as DIY renovators. Of these, 527 (61.4%) reported asbestos exposure during home renovations, 337 (39.3%) reported that their partner had been exposed to asbestos during renovations, and 196 (22.8%) reported that their children had been exposed. More than 20% of renovators planned to further renovate their current homes within the next 5 years. CONCLUSIONS: Self-reported asbestos exposure during home renovation is common. This preventable exposure could place adults and children at risk of MM many years into the future. Although such exposure is self-reported and ideally should be verified, this study identifies a potentially important problem in NSW.

Association of biomarker levels with severity of asbestos-related diseases.

OBJECTIVES: Asbestos-related diseases (ARDs) have increased globally over the decades, causing an economic burden and increased health care costs. It is difficult to predict the risk of development of ARDs and of respiratory disability among workers with a history of asbestos exposure. Blood based biomarkers have been reported as promising tools for the early detection of malignant mesothelioma. This study investigated whether serum soluble mesothelin-related peptide (SMRP) would reflect severity of disablement in compensable ARDs. METHODS: SMRP levels were measured in a cohort of 514 asbestos-exposed subjects. Severity of ARDs was assessed by a Medical Authority comprising four specially qualified respiratory physicians. Severity of ARDs and SMRP levels were compared. RESULTS: Mean (standard deviation) serum SMRP level in the population with compensable ARDs (n = 150) was 0.95 (0.65) nmol/L, and was positively associated with disability assessment (p = 0.01). Mean SMRP level in healthy asbestos-exposed subjects was significantly lower than those with pleural plaques (p < 0.0001) and in subjects with ARDs who received compensation (p < 0.01). CONCLUSION: This study indicates that serum SMRP levels correlate with severity of compensable ARDs. Serum SMRP could potentially be applied to monitor progress of ARDs. Further prospective work is needed to confirm the relationship between SMRP and disability assessment in this population.

Evaluation of ovarian cancer biomarkers in subjects with benign asbestos-related pleural diseases.

BACKGROUND: Mesothelioma and ovarian cancer have been reported to have a similar pathogenesis, and for this reason it was hypothesized that there may be biomarkers in common and possibly associated with benign pleural diseases caused by asbestos exposure. METHODS: Serum biomarkers including insulin-like growth factor-II (IGF-II), leptin, prolactin and vascular endothelial growth factor (VEGF) were measured in an observational study of subjects with benign asbestos-related pleural diseases (BARPD) (n=24) and healthy subjects with an asbestos exposure history (n=12). RESULTS: Mean serum IGF-II and VEGF concentration in healthy subjects with a history of asbestos exposure were higher than those with BARPD. Mean serum concentrations of leptin and prolactin showed opposite trends when compared to IGF-II and VEGF concentrations among these groups. CONCLUSIONS: The results suggest that IGF-II and VEGF concentrations are lower in BARPD, similar to studies of ovarian cancer. This finding warrants further investigation with malignant asbestos-related diseases.

Occupational exposure to asbestos in New South Wales, Australia (1970-1989): development of an asbestos task exposure matrix.

OBJECTIVES: To design and construct a standardised tool to provide exposure information associated with commonly used asbestos products and their related tasks in New South Wales (NSW), Australia. METHODS: Asbestos dust exposure measurements taken during workplace inspections in the 1970s and 1980s were collected and stored in an exposure database. Measurements were assigned to specific asbestos product and task groups and divided into two sampling periods 1970-1979 and 1980-1989. RESULTS: A total of 1578 asbestos air measurements collected from WorkCover and Dust Diseases Board company records were entered into a custom built exposure database. An asbestos-specific exposure matrix (ASTEM) was constructed in Microsoft Excel 2000, consisting of 3 axes incorporating 12 tasks, 8 asbestos products and the 2 time periods based on 872 individual measurements extracted from the exposure database. Each matrix cell contains the mean asbestos exposure levels measured in fibres/ml, 5th and 95th percentiles and number of data points in the set. CONCLUSION: An ASTEM has been developed which provides exposure levels for different task/product combinations. When used in conjunction with a detailed occupational history, it will improve exposure estimates of a worker's cumulative asbestos exposure.

Factors affecting soluble mesothelin related protein levels in an asbestos-exposed population.

BACKGROUND: Soluble mesothelin-related protein (SMRP) is increased in the sera of patients with malignant mesothelioma (MM), and has been suggested as a diagnostic tool for MM in an asbestos exposed population. However, factors affecting SMRP concentrations in normal subjects and those with other asbestos related disorders have not been investigated in any large population based study. METHODS: Five hundred and thirty-eight subjects with a history of asbestos exposure were studied. Age, height, weight, body mass index (BMI), serum creatinine and glucose, estimated glomerular filtration rate (eGFR) and lung function were compared with SMRP concentrations. RESULTS: The mean age [+/- standard deviation (SD)] of participants was 66.9 (+/-10.1) years, and mean (+/-SD) serum SMRP concentration was 0.91 (+/-0.67) nmol/L. SMRP values were inversely associated with weight (Pearson r=-0.1254, p=0.0036), BMI (Pearson r=-0.1594, p=0.0002), blood glucose (Pearson r=-0.1515, p=0.0004), single-breath carbon monoxide diffusing capacity (DLco) % predicted (Pearson r=-0.1847, p<0.0001), eGFR (Pearson r=-0.2835, p<0.0001) and single-breath carbon monoxide diffusing capacity per unit alveolar volume (DLco/VA)% predicted (Pearson r=-0.1872, p<0.0001) but were positively associated with age (Pearson r=0.2315, p<0.0001) and creatinine (Pearson r=0.3833, p<0.0001). CONCLUSIONS: This study has shown that demographic variables, physiological factors and lung function are associated with serum SMRP concentrations. Confounding factors should be considered when interpreting serum SMRP.

Exhaled breath condensate biomarkers in asbestos-related lung disorders.

OBJECTIVES: Asbestos induces generation of reactive oxygen and nitrogen species in laboratory studies. Several such species can be measured non-invasively in humans in exhaled breath condensate (EBC) but few have been evaluated. This study aimed to assess oxidative stress and lung inflammation in vivo. METHODS: Eighty six men were studied: sixty subjects with asbestos-related disorders (asbestosis: 18, diffuse pleural thickening (DPT): 16, pleural plaques (PPs): 26) and twenty six age- and gender-matched normal individuals. RESULTS: Subjects with asbestosis had raised EBC markers of oxidative stress compared with normal controls [8-isoprostane (geometric mean (95% CI) 0.51 (0.17-1.51) vs 0.07 (0.04-0.13) ng/ml, p<0.01); hydrogen peroxide (13.68 (8.63-21.68) vs 5.89 (3.99-8.69) microM, p<0.05), as well as increased EBC total protein (17.27 (10.57-28.23) vs 7.62 (5.13-11.34) microg/ml, p<0.05), and fractional exhaled nitric oxide (mean+/-SD) (9.67+/-3.26 vs 7.57+/-1.89ppb; p<0.05). EBC pH was lower in subjects with asbestosis compared with subjects with DPT (7.26+/-0.31 vs 7.53+/-0.24; p<0.05). There were no significant differences in exhaled carbon monoxide, EBC total nitrogen oxides and 3-nitrotyrosine between any of the asbestos-related disorders, or between these and controls. CONCLUSION: In asbestos-related disorders, markers of inflammation and oxidative stress are significantly elevated in subjects with asbestosis compared with healthy individuals but not in pleural diseases.

Osteopontin levels in an asbestos-exposed population.

PURPOSE: Serum osteopontin levels in patients with malignant mesothelioma have been reported to be higher than in healthy subjects. This study assessed serum osteopontin levels in an asbestos-exposed population to test whether nonmalignant asbestos-related disorders could influence osteopontin levels. EXPERIMENTAL DESIGN: This cross-sectional study evaluated serum osteopontin levels in 525 male subjects. Subjects were classified into six different diagnostic groups, including asbestosis (n=23), silicosis (n=20), diffuse pleural thickening (n=110), asbestosis and diffuse pleural thickening (n=13), pleural plaques (n=142), and healthy subjects with a history of asbestos exposure (n=217). RESULTS: Mean serum osteopontin levels differed among the six groups (P<0.0001). Mean osteopontin values of the healthy individuals exposed to asbestos were significantly different from that of subjects with asbestosis (P<0.001) and diffuse pleural thickening (P<0.001). There was a significant difference in mean serum levels of osteopontin in healthy individuals exposed to asbestos (n=217) compared with the group mean of all subjects with asbestos-related disorders (n=288; P<0.0001). CONCLUSIONS: Our results suggest that osteopontin levels are elevated in subjects with asbestos-related disorders without malignant mesothelioma. These data indicate that osteopontin, although reported to be useful for detecting malignant mesothelioma in asbestos-exposed individuals, may be influenced by nonmalignant processes.

Asbestos-related occupational lung diseases in NSW, Australia and potential exposure of the general population.

Asbestos is a fibrous silicate which is recognized as causing a variety of lung disorders including malignant mesothelioma of the pleura, lung cancer and asbestosis. Asbestos use has been banned in most developed countries but exposure still occurs under strict regulation in occupational settings and also occasionally in domestic settings. Although the hazards of asbestos are well known in developed countries, awareness of its adverse health effects is less in other parts of the world, particularly when exposure occurs in non-occupational settings. Experience of asbestos use and its adverse heath effects in developed countries such as Australia have resulted in development of expertise in the diagnosis and treatment of asbestos-related diseases as well as in screening and this can be used to help developing countries facing the issue of asbestos exposure.

Clinical consequences of asbestos-related diffuse pleural thickening: A review.

Asbestos-related diffuse pleural thickening (DPT), or extensive fibrosis of the visceral pleura secondary to asbestos exposure, is increasingly common due to the large number of workers previously exposed to asbestos. It may coexist with asbestos related pleural plaques but has a distinctly different pathology. The pathogenesis of this condition as distinct from pleural plaques is gradually becoming understood. Generation of reactive oxygen and nitrogen species, profibrotic cytokines and growth factors in response to asbestos is likely to play a role in the formation of a fibrinous intrapleural matrix. Benign asbestos related pleural effusions commonly antedate the development of diffuse pleural thickening. Environmental as well as occupational exposure to asbestos may also result in pleural fibrosis, particularly in geographic areas with naturally occurring asbestiform soil minerals. Pleural disorders may also occur after household exposure. High resolution computed tomography (CT) is more sensitive and specific than chest radiography for the diagnosis of diffuse pleural thickening, and several classification systems for asbestos-related disorders have been devised. Magnetic resonance imaging and fluorodeoxyglucose positron emission tomography (PET) scanning may be useful in distinguishing between DPT and malignant mesothelioma. DPT may be associated with symptoms such as dyspnoea and chest pain. It causes a restrictive defect on lung function and may rarely result in respiratory failure and death. Treatment is primarily supportive.

Soluble mesothelin-related protein in an asbestos-exposed population: the dust diseases board cohort study.

RATIONALE: Soluble mesothelin-related protein (SMRP) is raised in epithelial-type malignant mesothelioma (MM), but the utility of SMRP in screening for MM is unknown. OBJECTIVES: We aimed to evaluate SMRP in an asbestos-exposed cohort. METHODS: A total of 538 subjects were studied. Those with elevated SMRP (> or =2.5 nM) underwent further investigation including positron emission tomography/computed tomography. MEASUREMENTS AND MAIN RESULTS: Mean (+/-SD) SMRP in healthy subjects exposed to asbestos (n = 223) was 0.79 (+/-0.45) nM. Fifteen subjects had elevated SMRP, of whom one had lung cancer, which was successfully resected. Another with lung cancer was undetected by SMRP. No subjects were diagnosed with MM. Mean SMRP in healthy subjects was significantly lower than in subjects with pleural plaques alone (P < 0.01). CONCLUSIONS: This is the first large-scale prospective study of SMRP for screening for malignancy in asbestos-exposed individuals. A high false-positive rate was observed. SMRP seems unlikely to prove useful in screening for MM.

Incidence trends and gender differences in malignant mesothelioma in New South Wales, Australia.

OBJECTIVES: Features of malignant mesothelioma reportedly differ between men and women, including occupational asbestos exposure, histological subtype, and median survival. In this study, incidence trends and clinical features for malignant mesothelioma were compared between genders in New South Wales (NSW), where notification of malignant mesothelioma to the Central Cancer Registry is a statutory requirement. METHODS: Notifications to the Central Cancer Registry were compared with those to the registry of the NSW Workers' Compensation (Dust Diseases) Board. The latter includes occupational and clinical data. RESULTS: Of the 3090 cases of malignant mesothelioma reported to the Central Cancer Registry between 1972 and 2004, 456 (15%) were female. Altogether 1995 malignant mesotheliomas were compensated between 1969 and 2004, of which 105 (5%) occurred among women. The incidence increased for both genders by approximately 15-fold. Median survival was similar for the men and women for all of the cases (7 versus 6 months), but was better among the women who received compensation (8.5 versus 10.4 months, P<0.0001). The mean disease latency (42.8 years) increased over the study period (P<0.001). CONCLUSIONS: In New South Wales over the last 30 years, the total number of malignant mesotheliomas and the number of compensated cases of malignant mesothelioma have risen for both genders. The mean latency is increasing, and increasing numbers of "nonoccupational" cases are being reported. Survival remains poor.