Low dose CT detected interstitial lung abnormalities in a population with low asbestos exposure.

BACKGROUND: The use of low dose CT (LDCT) chest is becoming more widespread in occupationally exposed populations. There is a knowledge gap as to heterogeneity in severity and the natural course of asbestosis after low levels of exposure. This study reports the characteristics of LDCT-detected interstitial lung abnormalities (ILA). METHODS: The Asbestos Review Program offers annual LDCT, health assessments, and pulmonary function tests to an asbestos-exposed cohort. Asbestosis was defined using the Helsinki Consensus statement and the presence of ILA defined using a protocol for occupational CT reports. At least two of three pulmonary function tests: forced expiratory volume in 1 s (FEV1 );​ forced vital capacity (FVC); and diffusion capacity for carbon monoxide (DLco) were required for analysis of physiological decline. RESULTS: From 1513 cases, radiological ILA was present in 485 (32%). The cohort was 83.5% male with a median age of 68.3 years and a median (IQR) asbestos exposure of 0.7 (0.09-2.32) fiber/ml-year. A mixed occupation, mixed asbestos fiber cohort comprised the majority of the cohort (65.8%). Of those with ILA, 40 (8.2%) had an FVC decline of ≥10% and 30 (6.2%) had a DLco decline of ≥15% per year. Time since first exposure, increasing tobacco exposure and reported dyspnea were independently associated with the presence of ILA. CONCLUSIONS: In this population with relatively low asbestos exposure, LDCT-detected ILA that fits criteria for asbestosis is common, but physiological decline is not. This mild chronic stable phenotype of asbestos-associated ILA contrasts with the traditionally accepted views that asbestosis requires high exposures.

Comparison of outcomes following a cytological or histological diagnosis of malignant mesothelioma.

BACKGROUND: Survival with the epithelioid subtype of malignant mesothelioma (MM) is longer than the biphasic or sarcomatoid subtypes. There is concern that cytology-diagnosed epithelioid MM may underdiagnose the biphasic subtype. This study examines survival differences between patients with epithelioid MM diagnosed by cytology only and other subtypes diagnosed by histology. METHODS: Demographics, diagnosis method, MM subtype and survival were extracted from the Western Australia (WA) Mesothelioma Registry, which records details of all MM cases occurring in WA. RESULTS: A total of 2024 MM cases were identified over 42 years. One thousand seven hundred forty-four (86.2%) were male, median (IQR) age was 68.6 (60.4-77.0) years. A total of 1212 (59.9%) cases were identified as epithelioid subtype of which 499 (41.2%) were diagnosed using fluid cytology only. Those with a cytology-only diagnosis were older than the histology group (median 70.2 vs 67.6 years, P<0.001), but median survival was similar (cytology 10.6 (5.5-19.2) vs histology 11.1 (4.8-19.8) months, P=0.727) and Cox regression modelling adjusting for age, sex, site and time since first exposure showed no difference in survival between the different diagnostic approaches. CONCLUSIONS: Survival of cytologically and histologically diagnosed epithelioid MM cases does not differ. A diagnostic tap should be considered adequate to diagnose epithelioid MM without need for further invasive testing.

Estimation of quantitative levels of diesel exhaust exposure and the health impact in the contemporary Australian mining industry.

OBJECTIVES: To estimate quantitative levels of exposure to diesel exhaust expressed by elemental carbon (EC) in the contemporary mining industry and to describe the excess risk of lung cancer that may result from those levels. METHODS: EC exposure has been monitored in Western Australian miners since 2003. Mixed-effects models were used to estimate EC levels for five surface and five underground occupation groups (as a fixed effect) and specific jobs within each group (as a random effect). Further fixed effects included sampling year and duration, and mineral mined. On the basis of published risk functions, we estimated excess lifetime risk of lung cancer mortality for several employment scenarios. RESULTS: Personal EC measurements (n=8614) were available for 146 different jobs at 124 mine sites. The mean estimated EC exposure level for surface occupations in 2011 was 14 µg/m3 for 12 hour shifts. Levels for underground occupation groups ranged from 18 to 44 µg/m3. Underground diesel loader operators had the highest exposed specific job: 59 µg/m3. A lifetime career (45 years) as a surface worker or underground miner, experiencing exposure levels as estimated for 2011 (14 and 44 µg/m3 EC), was associated with 5.5 and 38 extra lung cancer deaths per 1000 males, respectively. CONCLUSIONS: EC exposure levels in the contemporary Australian mining industry are still substantial, particularly for underground workers. The estimated excess numbers of lung cancer deaths associated with these exposures support the need for implementation of stringent occupational exposure limits for diesel exhaust.

Trends in exposure to respirable crystalline silica (1986-2014) in Australian mining.

BACKGROUND: Respirable crystalline silica (RCS) has been associated with severe health risks. Exposures in Western Australia (WA) have been typically high in hard-rock mining and have reduced substantially since the mid-1900s. We described trends in RCS exposure in WA miners over the past 30 years. METHODS: A total of 79 445 reported personal RCS exposure measurements, covering the years 1986-2014, were examined. Mixed-effects models were applied to estimate RCS exposure levels, including spline terms to estimate a time trend. RESULTS: An overall downward trend of about -8% per year was observed for RCS exposures in WA mining. Highest RCS exposure levels were modeled for base metal mining and exploration settings. Drilling occupations were among the highest exposed jobs. CONCLUSION: RCS exposure levels have fallen considerably in the last three decades. However, there are still mining occupations that may need further attention to avoid adverse health effects in these workers.

Effect of N-acetylcysteine supplementation on oxidative stress status and alveolar inflammation in people exposed to asbestos: a double-blind, randomized clinical trial.

BACKGROUND AND OBJECTIVE: Many of the pathological consequences in the lung following inhalation of asbestos fibres arise as a consequence of persistent oxidative stress and inflammation. Inflammatory responses can be observed in asymptomatic asbestos-exposed individuals. There are currently no interventions to reduce inflammatory or oxidative responses to asbestos before disease develops. We investigated the effects of oral N-acetylcysteine (NAC) on indicators of inflammation or oxidative stress in asymptomatic people previously exposed to asbestos. METHODS: A double-blind, randomized, placebo-controlled study was conducted to assess the effectiveness and safety of 1800 mg of NAC given orally over a period of 4 months. This was a proof of principle study. Effectiveness was assessed using indicators of inflammation or oxidation as primary end-points. Serum levels of total combined thiols (cysteine, cysteinylglycine, glutathione and homocysteine) were used to monitor the NAC supplementation. RESULTS: Thirty-four subjects were randomly allocated to NAC and 32 to placebo. Serum levels of total combined thiols were similar between the groups after intervention. There were no differences in levels of inflammatory or oxidative stress end-points between the groups. No adverse effects were identified. CONCLUSIONS: No evidence was found that NAC supplementation replenishes total combined thiols in the blood of healthy subjects with a history of asbestos exposure. There was also no evidence of reduced indicators of inflammation or oxidative stress. Further studies should determine the conditions required to increase levels of total anti-oxidant capacity in the blood and in the lungs of subjects with either asbestos-related diseases or subclinical lung inflammation.

Familial aggregation of malignant mesothelioma in former workers and residents of Wittenoom, Western Australia.

Clustering of cases of malignant mesothelioma within families has often been observed, but disentangling genetic and exposure effects has not been done. Former workers and residents exposed to crocidolite at Wittenoom, Western Australia, where many families shared exposure to asbestos, have had high rates of mesothelioma. Our study aimed to estimate the additional risk of mesothelioma in relatives, after allowance for common exposure to crocidolite. More than 11,000 former asbestos workers and residents from Wittenoom have been followed up in cancer and death registries. Levels of exposure for all members of the Wittenoom cohorts have been estimated previously. Relationships between family members of all mesothelioma cases were established from questionnaires, birth and death certificates. Expected numbers of cases of mesothelioma were estimated by fitting a Weibull survival model to all data, based on time from first asbestos exposure, duration and intensity of exposure and age. For each family group, the earliest case was considered the index case. Predicted risk was estimated for each subject from the time of diagnosis of the index case. Familial risk ratios were estimated by dividing observed cases by the sum of risks of all same degree relatives of index cases. There were 369 family groups with at least one case of mesothelioma and a further 25 cases of mesothelioma among relatives in the same families, with 12.9 expected. The risk ratio for blood relatives was 1.9 (95% confidence interval [CI] = 1.3-2.9, p = 0.002). These findings suggest an important, but not large, genetic component in mesothelioma, similar to many other cancers.

Rationale, design and methods for a community-based study of clustering and cumulative effects of chronic disease processes and their effects on ageing: the Busselton healthy ageing study.

BACKGROUND: The global trend of increased life expectancy and increased prevalence of chronic and degenerative diseases will impact on health systems. To identify effective intervention and prevention strategies, greater understanding of the risk factors for and cumulative effects of chronic disease processes and their effects on function and quality of life is needed.The Busselton Healthy Ageing Study aims to enhance understanding of ageing by relating the clustering and interactions of common chronic conditions in adults to function. Longitudinal (3-5 yearly) follow-up is planned. METHODS/DESIGN: Phase I (recruitment) is a cross-sectional community-based prospective cohort study involving up to 4,000 'Baby Boomers' (born from 1946 to 1964) living in the Busselton Shire, Western Australia. The study protocol involves a detailed, self-administered health and risk factor questionnaire and a range of physical assessments including body composition and bone density measurements, cardiovascular profiling (blood pressure, ECG and brachial pulse wave velocity), retinal photography, tonometry, auto-refraction, spirometry and bronchodilator responsiveness, skin allergy prick tests, sleep apnoea screening, tympanometry and audiometry, grip strength, mobility, balance and leg extensor strength. Cognitive function and reserve, semantic memory, and pre-morbid intelligence are assessed. Participants provide a fasting blood sample for assessment of lipids, blood glucose, C-reactive protein and renal and liver function, and RNA, DNA and serum are stored. Clinically relevant results are provided to all participants. The prevalence of risk factors, symptoms and diagnosed illness will be calculated and the burden of illness will be estimated based on the observed relationships and clustering of symptoms and illness within individuals. Risk factors for combinations of illness will be compared with those for single illnesses and the relation of combinations of illness and symptoms to cognitive and physical function will be estimated. DISCUSSION: This study will enable a thorough characterization of multiple disease processes and their risk factors within a community-based sample of individuals to determine their singular, interactive and cumulative effects on ageing. The project will provide novel cross-sectional data and establish a cohort that will be used for longitudinal analyses of the genetic, lifestyle and environmental factors that determine whether an individual ages well or with impairment.

Association between diesel engine exhaust exposure and lung function in Australian gold miners.

Previous studies have reported that miners (and other workers) exposed to high levels of diesel engine exhaust (DEE) have an increased risk of lung function decline. The main objective of this study was to evaluate associations between exposure to different components associated with DEE in relation to lung function across a 12-h working shift. Eighty underground gold miners and twenty surface miners completed spirometry and questionnaires at the beginning and end of their 12 h work shift. Personal exposure to elemental carbon (EC), volatile organic compounds (VOCs), nitrogen dioxide (NO2), particle size and particle number were monitored during their shift. Multiple regression models were used to examine the associations between DEE and lung function, adjusting for a range of covariates. Underground miners were exposed to higher levels of EC, VOCs, NO2, and particle number and larger mean particle size than surface miners. Cross-shift reduction in Z-score value of FEV1/FVC in underground miners was statistically significantly greater than those of surface miners. The cross-shift change in Z-score value of FEV1/FVC was associated with exposure to higher concentration of EC and particle number, but not with VOCs, NO2 and particle size. Occupational exposure to diesel engine exhaust in current Australian gold mines is substantial. Exposures were higher in underground miners and had a negative association with their lung function over a single 12-h shift.

Cancer incidence in the Western Australian mining industry (1996-2013).

BACKGROUND: Miners are frequently exposed to established and potential carcinogens. We aimed to assess cancer incidence in miners relative to the general population and identify high-risk subgroups. METHODS: Incident cancers in Western Australian miners (n=153,922; 86% male) during 1996-2013 were identified. Indirectly standardised incidence ratios (SIRs) were calculated and mixed-effects Poisson models were used to calculate Incidence Rate Ratios (IRRs) to identify high-risk within-cohort subgroups. RESULTS: Compared with the general population, the overall cancer incidence in miners (n=4194 cases) was lower for both females (SIR:0.83, 95%CI:0.74-0.92) and males (SIR:0.96, 95%CI:0.93-0.99). Overall, cancer incidence did not differ by employment duration or employment commencement time. Ever-underground work was associated with lung cancer (IRR:1.81, 95%CI:1.11-2.93). Relative to multi-ore miners, IRRs for specific cancers were significantly different when exclusively mining: iron (prostate:0.73, 95%CI:0.56-0.94); gold (lung:1.77, 95%CI:1.04-3.01 and colorectum:1.70, 95%CI:1.16-2.51); and other metals (urinary tract:1.85, 95%CI:1.03-3.31 and leukaemia:0.36, 95%CI:0.14-0.96). CONCLUSION: Working underground emerged as a significant determinant of lung cancer risk in our contemporary mining cohort. Increased risks of lung, prostate, colorectal and urinary tract cancers and leukaemia were identified in miners of specific ores. These findings underline the importance of continued surveillance of the health and exposures of this relatively young cohort of miners.