Anthony R. Johnson

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.

Projected mesothelioma incidence in men in New South Wales

Objectives: Based on observed numbers of incident mesotheliomas since 1972, to predict future numbers in men in New South Wales. Methods: The incidence of mesothelioma was modelled in two ways. First by using an age/birth cohort model, and second by using a model based on potential exposure to asbestos in terms of age and calendar year. The latter model included a term for clearance of asbestos fibres from the lungs, and a term for diagnostic fraction. The age and calendar year model was based on the model introduced by Hodgson and colleagues but replaced piecewise effects by smooth functions represented by cubic splines. Results: The number of mesotheliomas between 2004 and 2060 was predicted as 6690 with the age-cohort model and as 6779 by the age and calendar year model, with peak annual numbers of 187 in the year 2021 and 196 in the year 2014 with the two models respectively. Conclusions: The pattern of parameter estimates in the two models was in accord with the known use of amphibole asbestos in Australia. The predicted peak year of 201421 is 3035 years after the phasing out of amphibole use, and this period is in accord with predictions for the UK and the US; in the latter country the peak was 1015 years earlier corresponding to a marked decline of amphibole use in and following the 1960s.

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.

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.

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

Abstract 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. Clin Chem Lab Med 2010;48:869–74.

Fractional exhaled nitric oxide concentration is increased in asbestosis and pleural plaques

Objective and background:  Asbestos exposure induces generation of reactive oxygen and nitrogen species. Nitric oxide is involved in asbestos‐related lung toxicity in vitro and can be measured non‐invasively in humans in exhaled breath. The authors hypothesized that fractional exhaled nitric oxide concentration (FENO) would be increased in subjects with asbestos‐related lung disorders.

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.

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 workers cumulative asbestos exposure.

Surveillance of Australian workplace Based Respiratory Events (SABRE) in New South Wales

BACKGROUND The Surveillance of Australian workplace Based Respiratory Events (SABRE) New South Wales (NSW) scheme is a voluntary notification scheme established to determine the incidence of occupational lung diseases in NSW Australia. AIMS Data presented in this paper summarize the last 7 years of reporting to SABRE (June 2001 to December 2008). METHODS Every 2 months, participating occupational physicians, respiratory physicians and general practitioners (accredited by the NSW WorkCover Authority) reported new cases of occupational lung disease seen in their practices. Data collected include gender, age, causal agent and the occupations and industries believed responsible. Estimated incidence was calculated for each disease. RESULTS Three thousand six hundred and fifty-four cases were notified to the scheme, consisting of 3856 diagnoses. Most of the cases were males (76%). Pleural plaques [1218 (28%)] were the most frequently reported condition, followed by mesothelioma [919 (24%)]. Silicosis [90 (2%)] and occupational asthma [OA; 89 (2%)] were the most frequently reported non-asbestos-related diseases. Estimated rates for mesothelioma, diffuse pleural thickening (DPT) and OA were 83, 83 and 5 cases per million employed males per year, respectively. Trades such as carpenters and electricians associated with the building industry, electricity supply and asbestos product manufacture were the most common occupations and industries reported. CONCLUSIONS Asbestos-related diseases are the most frequently reported conditions to SABRE NSW. The very low incidence of OA for NSW most likely reflects under-diagnosis as well as under-reporting. Occupational lung disease is still occurring in NSW despite current preventative strategies. The SABRE scheme currently provides the only available information in this area.