Regulatory T cells mediate specific suppression by depleting peptide-MHC class II from dendritic cells.

Regulatory T cells (Treg cells) can activate multiple suppressive mechanisms in vitro after activation via the T cell antigen receptor, resulting in antigen-independent suppression. However, it remains unclear whether similar pathways operate in vivo. Here we found that antigen-specific Treg cells activated by dendritic cells (DCs) pulsed with two antigens suppressed conventional naive T cells (Tnaive cells) specific for both cognate antigens and non-cognate antigens in vitro but suppressed only Tnaive cells specific for cognate antigen in vivo. Antigen-specific Treg cells formed strong interactions with DCs, resulting in selective inhibition of the binding of Tnaive cells to cognate antigen yet allowing bystander Tnaive cell access. Strong binding resulted in the removal of the complex of cognate peptide and major histocompatibility complex class II (pMHCII) from the DC surface, reducing the capacity of DCs to present antigen. The enhanced binding of Treg cells to DCs, coupled with their capacity to deplete pMHCII, represents a novel pathway for Treg cell-mediated suppression and may be a mechanism by which Treg cells maintain immune homeostasis.

Polyclonally Derived Alloantigen-Specific T Regulatory Cells Exhibit Target-Specific Suppression and Capture MHC Class II from Dendritic Cells.

Foxp3+ T regulatory (Treg) cells prevent allograft rejection and graft-versus-host disease. Although polyclonal Tregs have been used both in animal models and in humans, the fine specificity of their suppressive function is poorly defined. We have generated mouse recipient-derived alloantigen-specific Tregs in vitro and explored the fine specificity of their suppressive function and their mechanism of action in vitro and in vivo. In vitro, when alloantigen and peptide Ag were both presented on the same dendritic cell, both responses were suppressed by iTregs specific either for the alloantigen or for the peptide Ag. In vivo, iTreg suppression was limited to the cognate Ag, and no bystander suppression was observed when both allo-antigen and peptide Ag were present on the same dendritic cell. In vitro, alloantigen-specific Tregs captured cognate MHC but failed to capture noncognate MHC. Our results demonstrate that a polyclonal population of iTregs generated from naive T cells can mediate highly specific function in vivo and support the view that Treg therapy, even with unselected polyclonal populations, is likely to be target antigen-specific and that bystander responses to self-antigens or to infectious agents are unlikely.

Psychometric properties of the Perceived Stress Scale (PSS-10) in silica-exposed workers from diverse cultural and linguistic backgrounds.

BACKGROUND: The Perceived Stress Scale (PSS-10) has been used in a range of occupational cohorts, but only recently in stone benchtop workers undergoing screening for silicosis. The aim of this study was to compare psychometric properties of the PSS-10 in stone benchtop workers amongst those born overseas or who used an interpreter. METHODS: Stone benchtop workers in Melbourne, Australia completed the PSS-10 as part of their occupational screening for silicosis. Internal consistency was assessed with Cronbach's α for the total score and the positive and negative subscales. Validity was assessed using confirmatory factor analysis (CFA). Analysis was performed for the total group and for subgroups according to sex, interpreter use, overseas-born, and language spoken at home. RESULTS: The results of 682 workers with complete PSS-10 scores were included in analysis. Most participants were male (93%), with mean age 36.9 years (SD 11.4), with just over half (51.6%) born in Australia, 10.1% using an interpreter, and 17.5% using a language other than English at home. Cronbach's α for the overall group (α = 0.878) suggested good internal consistency. DISCUSSION: CFA analysis for validity testing suggested PSS-10 performance was good for both sexes, moderate for country of birth and language spoken at home categories, but poorer for those who used an interpreter. Whilst professional interpreters provide a range of benefits in the clinical setting, the use of translated and validated instruments are important, particularly in cohorts with large numbers of migrant workers. CONCLUSION: This study describes the psychometric properties of the PSS-10 in a population of stone benchtop workers, with good internal consistency, and mixed performance from validity testing across various subgroups.

Chest x-ray has low sensitivity to detect silicosis in artificial stone benchtop industry workers.

BACKGROUND AND OBJECTIVE: Chest x-ray (CXR) remains a core component of health monitoring guidelines for workers at risk of exposure to crystalline silica. There has however been a lack of evidence regarding the sensitivity of CXR to detect silicosis in artificial stone benchtop industry workers. METHODS: Paired CXR and high-resolution computed tomography (HRCT) images were acquired from 110 artificial stone benchtop industry workers. Blinded to the clinical diagnosis, each CXR and HRCT was independently read by two thoracic radiologists from a panel of seven, in accordance with International Labour Office (ILO) methodology for CXR and International Classification of HRCT for Occupational and Environmental Respiratory Diseases. Accuracy of screening positive (ILO major category 1, 2 or 3) and negative (ILO major category 0) CXRs were compared with identification of radiological features of silicosis on HRCT. RESULTS: CXR was positive for silicosis in 27/110 (24.5%) workers and HRCT in 40/110 (36.4%). Of the 83 with a negative CXR (ILO category 0), 15 (18.1%) had silicosis on HRCT. All 11 workers with ILO category 2 or 3 CXRs had silicosis on HRCT. In 99 workers ILO category 0 or 1 CXRs, the sensitivity of screening positive CXR compared to silicosis identified by HRCT was 48% (95%CI 29-68) and specificity 97% (90-100). CONCLUSION: Compared to HRCT, sensitivity of CXR was low but specificity was high. Reliance on CXR for health monitoring would provide false reassurance for many workers, delay management and underestimate the prevalence of silicosis in the artificial stone benchtop industry.

The carcinogenicity of opium consumption: a systematic review and meta-analysis.

The carcinogenicity of opium consumption was recently evaluated by a Working Group convened by the International Agency for Research on Cancer (IARC). We supplement the recent IARC evaluation by conducting an extended systematic review as well as a quantitative meta-analytic assessment of the role of opium consumption and risk for selected cancers, evaluating in detail various aspects of study quality on meta-analytic findings. We searched the published literature to identify all relevant studies on opium consumption and risk of selected cancers in humans through 31 October, 2022. Meta-relative risks (mRRs) and associated 95% confidence intervals (CIs) were estimated using random-effects models for studies of cancer of the urinary bladder, larynx, lung, oesophagus, pancreas, and stomach. Heterogeneity among studies was assessed using the I2 statistic. We assessed study quality and conducted sensitivity analyses to evaluate the impact of potential reverse causation, protopathic bias, selection bias, information bias, and confounding. In total, 2 prospective cohort studies and 33 case-control studies were included. The overall pooled mRR estimated for 'ever or regular' versus 'never' use of opium ranged from 1.50 (95% CI 1.13-1.99, I2 = 0%, 6 studies) for oesophageal cancer to 7.97 (95% CI 4.79-13.3, I2 = 62%, 7 studies) for laryngeal cancer. Analyses of cumulative opium exposure suggested greater risk of cancer associated with higher opium consumption. Findings were robust in sensitivity analyses excluding studies prone to potential methodological sources of biases and confounding. Findings support an adverse association between opium consumption and cancers of the urinary bladder, larynx, lung, oesophagus, pancreas and stomach.

Prevalence and risk factors for silicosis among a large cohort of stone benchtop industry workers.

OBJECTIVES: High silica content artificial stone has been found to be associated with silicosis among stone benchtop industry (SBI) workers. The objectives of this study were to determine the prevalence of and risk factors for silicosis among a large cohort of screened SBI workers, and determine the reliability of respiratory function testing (RFT) and chest x-ray (CXR) as screening tests in this industry. METHODS: Subjects were recruited from a health screening programme available to all SBI workers in Victoria, Australia. Workers undertook primary screening, including an International Labour Office (ILO) classified CXR, and subject to prespecified criteria, also underwent secondary screening including high-resolution CT (HRCT) chest and respiratory physician assessment. RESULTS: Among 544 SBI workers screened, 95% worked with artificial stone and 86.2% were exposed to dry processing of stone. Seventy-six per cent (414) required secondary screening, among whom 117 (28.2%) were diagnosed with silicosis (median age at diagnosis 42.1 years (IQR 34.8-49.7)), and all were male. In secondary screening, silicosis was associated with longer SBI career duration (12 vs 8 years), older age, lower body mass index and smoking. In those with silicosis, forced vital capacity was below the lower limit of normal in only 14% and diffusion capacity for carbon monoxide in 13%. Thirty-six (39.6%) of those with simple silicosis on chest HRCT had an ILO category 0 CXR. CONCLUSION: Screening this large cohort of SBI workers identified exposure to dry processing of stone was common and the prevalence of silicosis was high. Compared with HRCT chest, CXR and RFTs had limited value in screening this high-risk population.

Cancer and mortality in coal mine workers: a systematic review and meta-analysis.

Coal mine workers are exposed to a number of workplace hazards which may increase the risk of cancer and mortality. We conducted a systematic review and meta-analysis to investigate cancer and mortality in coal mine workers We searched in Ovid Medline, PubMed, Embase and Web of Science databases using keywords and text words related to coal mines, cancer and mortality and identified 36 full-text articles using predefined inclusion criteria. Each study's quality was assessed using the Newcastle-Ottawa Scale. We performed random-effect meta-analyses including 21 of the identified articles evaluating cancer and/or mortality of coal mine workers. The meta-analysis showed an increased risk of all-cause mortality (SMR 1.14, 95% CI 1.00 to 1.30) and mortality from non-malignant respiratory disease (NMRD) (3.59, 95% CI 3.00 to 4.30) in cohorts with coal workers' pneumoconiosis (CWP). We found a somewhat increased risk of stomach cancer (1.11, 95% CI 0.97 to 1.35) and of mortality from NMRD (1.26, 95% CI 0.99 to 1.61) in the cohorts of coal miners with unknown CWP status. The meta-analysis also showed a decreased risk of prostate cancer and cardiovascular and cerebrovascular mortality among coal miners. This may be a result of the healthy worker effect and possible lower smoking rates, and perhaps also reflect the physically active nature of many jobs in coal mines. The meta-analysis for lung cancer did not show increased risk in coal miners with CWP (1.49, 95% CI 0.70 to 3.18) or for coal miners of unknown CWP status (1.03, 95% CI 0.91 to 1.18). Lower smoking rates in coal mine workers could explain why case-control studies where smoking was controlled for showed higher risks for lung cancer than were seen in cohort studies. Coal mine workers are at increased risk of mortality from NMRD but decreased risk of prostate cancer and cardiovascular and cerebrovascular mortality. Studies of coal mine workers need long-term follow-up to identify increased mortality and cancer incidence.

Predictors of psychological stress in silica-exposed workers in the artificial stone benchtop industry.

BACKGROUND AND OBJECTIVE: Artificial stone benchtops are a popular kitchen product, but dust from their preparation and installation contains respirable crystalline silica, which causes silicosis. Silicosis is a preventable, permanent lung disease. The aim of this study was to assess mental health in workers from the artificial stone benchtop industry at risk of silicosis. METHODS: Workers from the artificial stone benchtop industry undergoing assessment for silica-associated disease were included. Information on demographics; occupational, medical and smoking history; modified Medical Research Council dyspnoea scale; Perceived Stress Scale (PSS-10) questionnaire; spirometry; and chest x-ray was collected. Univariate and multivariate regression analyses were conducted. RESULTS: Of the 547 participants, the majority were men, aged under 45 years, in the industry for less than 10 years. With each increase of dyspnoea score, PSS-10 scores increased. Higher PSS-10 scores were also observed in those no longer in the industry, with a history of anxiety or depression, attending assessment early in the programme and a medium exposure duration. Participants who used an interpreter reported lower stress. No difference was observed across job title, age, sex, smoking, spirometry or chest x-ray categories after multivariate analysis. CONCLUSION: This study identified workers with dyspnoea as likely to report higher stress. Other factors, such as leaving the industry, early attendance and a history of anxiety or depression, are also helpful in identifying workers at risk of poorer mental health outcomes.

Comparison of agreement in asthmagen exposure assessments between rule-based automatic algorithms and a job exposure matrix in healthcare workers in Australia and Bhutan.

BACKGROUND: Assessment of occupational exposures is an integral component of population-based studies investigating the epidemiology of occupational diseases. However, all the available methods for exposure assessment have been developed, tested and used in high-income countries. Except for a few studies examining pesticide exposures, there is limited research on whether these methods are appropriate for assessing exposure in LMICs. The aim of this study is to compare a task-specific algorithm-based method (OccIDEAS) to a job-specific matrix method (OAsJEM) in the assessment of asthmagen exposures among healthcare workers in a high-income country and a low- and middle- income country (LMIC) to determine an appropriate assessment method for use in LMICs for future research. METHODS: Data were obtained from a national cross-sectional survey of occupational asthmagens exposure in Australia and a cross-sectional survey of occupational chemical exposure among Bhutanese healthcare workers. Exposure was assessed using OccIDEAS and the OAsJEM. Prevalence of exposure to asthmagens and inter-rater agreement were calculated. RESULTS: In Australia, the prevalence was higher for a majority of agents when assessed by OccIDEAS than by the OAsJEM (13 versus 3). OccIDEAS identified exposures to a greater number of agents (16 versus 7). The agreement as indicated by κ (Cohen's Kappa coefficient) for six of the seven agents assessed was poor to fair (0.02 to 0.37). In Bhutan, the prevalence of exposure assessed by OccIDEAS was higher for four of the seven agents and κ was poor for all the four agents assessed (-0.06 to 0.13). The OAsJEM overestimated exposures to high-level disinfectants by assigning exposures to all participants from 10 (Bhutan) and 12 (Australia) ISCO-88 codes; whereas OccIDEAS assigned exposures to varying proportions of participants from these ISCO-codes. CONCLUSION: There was poor to fair agreement in the assessment of asthmagen exposure in healthcare workers between the two methods. The OAsJEM overestimated the prevalence of certain exposures. As compared to the OAsJEM, OccIDEAS appeared to be more appropriate for evaluating cross-country exposures to asthmagens in healthcare workers due to its inherent quality of assessing task-based determinants and its versatility in being adaptable for use in different countries with different exposure circumstances.

Migrant workers occupational health research: an OMEGA-NET working group position paper.

OBJECTIVE: The aims of the study were: (1) to clarify the definitions of "migrant" used in occupational health research; (2) to summarize migrant workers' industry sectors, occupations and employment conditions; (3) to identify the occupational health and safety services available to migrant workers; (4) to summarize work-related health problems found among migrant workers; (5) to identify the methodological challenges to research into occupational health of migrant workers; and (6) to recommend improvements in migrant occupational health research. METHODS: This position paper was prepared by researchers from several European countries and Australia, working within the EU COST Action OMEGA-NET. The paper drew on two recent systematic reviews on the occupational health of international migrant workers and other literature, and also identified uncertainties and gaps in the research literature. Migrants may, for example, be temporary or permanent, moving for specific jobs migrants or other reasons. Their ethnicity and language capabilities will affect their work opportunities. RESULTS: The occupational health literature seldom adequately identifies the heterogeneity or characteristics of the migrant group being studied. Migrants tend to work in more physically and mentally demanding environments with higher exposures than native workers. Migrants tend to have an increased risk of physical and mental ill health, but less access to health care services. This has been demonstrated recently by high rates of COVID-19 and less access to health care. There have been a number of cross-sectional studies of migrant health but few long-term cohort studies were identified. Other study designs, such as registry-based studies, surveys and qualitative studies may complement cross-sectional studies. Mixed-methodology studies would be valuable in research on migrants' occupational health. Language and lack of trust are barriers to migrant research participation. CONCLUSION: Targeted research, especially longitudinal, identifying how these economically important but often-vulnerable workers can be best assisted is needed. Researchers should identify the characteristics of the migrant workers that they are studying including visa/migration circumstances (temporary, permanent, undocumented), racial and ethnic characteristics, existing skills and language abilities.

Identification of early-stage silicosis through health screening of stone benchtop industry workers in Victoria, Australia.

OBJECTIVES: The popularity of high silica content artificial stone has been associated with emergence of severe, progressive silicosis as a major health issue affecting workers in the stone benchtop industry. This population-based health assessment programme has been implemented with the aim of identifcation of silica-associated disease at a preclinical stage. METHODS: All current and former workers from the stone benchtop industry in the State of Victoria are offered free health assessments. Primary evaluations include a standardised questionnaire, physical examination, spirometry and gas transfer assessment and International Labour Organisation-categorised chest X-ray. Secondary evaluations include high-resolution CT chest, blood tests and a respiratory physician evaluation. RESULTS: At the end of the first 12 months, 86/239 (36%) workers who had completed secondary evaluation were diagnosed with silicosis (65 simple silicosis and 21 complicated silicosis). 22 had worked in the industry for less than 10 years at the time of diagnosis. Of those with simple silicosis, 80% of workers reported breathlessness only with strenuous exercise (modified Medical Research Council score of 0), and lung function was well preserved (prebronchodilator forced vital capacity mean 99.8% predicted (SD 13.6), diffusion capacity of the lung for carbon monoxide mean 96.2% predicted (SD 18.0)). Antinuclear antibodies were detected in 37% with silicosis and 24% without silicosis. CONCLUSION: Early results from this comprehensive health assessment programme have indicated a high proportion of referred artificial stone benchtop workers have silicosis, including many with early-stage disease. The common finding of antinuclear antibodies suggest significant potential for autoimmune disease in this occupational group.

Type I interferon signaling attenuates regulatory T cell function in viral infection and in the tumor microenvironment.

Regulatory T cells (Tregs) play a cardinal role in the immune system by suppressing detrimental autoimmune responses, but their role in acute, chronic infectious diseases and tumor microenvironment remains unclear. We recently demonstrated that IFN-α/ß receptor (IFNAR) signaling promotes Treg function in autoimmunity. Here we dissected the functional role of IFNAR-signaling in Tregs using Treg-specific IFNAR deficient (IFNARfl/flxFoxp3YFP-Cre) mice in acute LCMV Armstrong, chronic Clone-13 viral infection, and in tumor models. In both viral infection and tumor models, IFNARfl/flxFoxp3YFP-Cre mice Tregs expressed enhanced Treg associated activation antigens. LCMV-specific CD8+ T cells and tumor infiltrating lymphocytes from IFNARfl/flxFoxp3YFP-Cre mice produced less antiviral and antitumor IFN-γ and TNF-α. In chronic viral model, the numbers of antiviral effector and memory CD8+ T cells were decreased in IFNARfl/flxFoxp3YFP-Cre mice and the effector CD4+ and CD8+ T cells exhibited a phenotype compatible with enhanced exhaustion. IFNARfl/flxFoxp3YFP-Cre mice cleared Armstrong infection normally, but had higher viral titers in sera, kidneys and lungs during chronic infection, and higher tumor burden than the WT controls. The enhanced activated phenotype was evident through transcriptome analysis of IFNARfl/flxFoxp3YFP-Cre mice Tregs during infection demonstrated differential expression of a unique gene signature characterized by elevated levels of genes involved in suppression and decreased levels of genes mediating apoptosis. Thus, IFN signaling in Tregs is beneficial to host resulting in a more effective antiviral response and augmented antitumor immunity.

Does exposure to workplace hazards cluster by occupational or sociodemographic characteristics? An analysis of foreign-born workers in Australia.

BACKGROUND: Disparities in exposure to occupational hazards may be linked to social position as well as the type of job a person holds. This study aimed to describe the prevalence of exposure to workplace hazards among three migrant worker groups and to assess whether social disparities in exposure for these groups remain after adjusting for occupational characteristics. METHODS: Data were collected in 2017/2018 from 1630 Australian workers born in New Zealand, India, and the Philippines. Weighted estimated prevalence of exposure to 10 carcinogens and four psychosocial hazards (discrimination, job strain, vulnerability, and insecurity) was calculated for sociodemographics and occupation. Regression estimated the likelihood of exposure by sociodemographics after adjustment for occupational characteristics. RESULTS: Exposure to workplace hazards ranged from 11.7% (discrimination) to 61.2% (exposed to at least one carcinogen). Compared with workers born in India, New Zealand born workers were over twice as likely to be exposed to diesel engine exhaust (adjusted odds ratio [aOR] = 2.60) and 60% more likely to be exposed to at least one carcinogen (aOR = 1.60) but less likely to be exposed to any psychosocial hazard. Social disparities by country of birth, sex, age, education, and number of years in Australia, as well as company size, employment type, and hours, worked remained associated with greater likelihood of reporting one or more workplace hazards after adjusting for occupational characteristics. CONCLUSION: Examining sociodemographic as well as occupational characteristics helps to clarify groups most likely to be exposed to workplace hazards who can be hidden when examining occupational characteristics alone.

The estimated prevalence of exposure to carcinogens, asthmagens, and ototoxic agents among healthcare workers in Australia.

BACKGROUND: Healthcare workers are occupationally exposed to various hazardous chemicals and agents that can potentially result in long-term adverse health effects. These exposures have not been comprehensively examined at a population level. The aim of this study was to examine occupational exposures to a wide range of asthmagens, carcinogens, and ototoxic agents among healthcare workers in Australia. METHODS: Data were collected as part of the Australian Work Exposures Studies, which were computer-assisted telephone surveys conducted in 2011, 2014, and 2016 to assess the prevalence of occupational exposures to carcinogens, asthmagens, and ototoxic agents, respectively, among Australian workers. Using data on healthcare workers, the prevalence of exposures to these agents was calculated and associations of demographic variables and occupation groups with exposure status were examined. RESULTS: The prevalence of exposure to at least one asthmagen, carcinogen, and ototoxic agent was 92.3%, 50.7%, and 44.6%, respectively. The most common exposures were to (a) cleaning and sterilizing agents in the asthmagen group; (b) shift work in the carcinogen group; and (c) toluene and p-xylene among ototoxic agents. Exposure varied by occupation, with exposure to carcinogens and ototoxic agents highest among personal carers and exposure to carcinogens most likely among nursing professionals and health and welfare support workers. CONCLUSION: The results demonstrate that a substantial proportion of Australian healthcare workers are occupationally exposed to asthmagens, carcinogens, and ototoxic agents. These exposures are more common among certain occupational groups. The information provided by this study will be useful in prioritizing and implementing control strategies.

TCR Signaling and CD28/CTLA-4 Signaling Cooperatively Modulate T Regulatory Cell Homeostasis.

Foxp3+ T regulatory cells (Tregs), conventional CD4+Foxp3- T cells, and CD8+ T cells represent heterogeneous populations composed of naive phenotype (NP, CD44low) and memory phenotype (MP, CD44high) subpopulations. NP and MP subsets differ in their activation state, contribution to immune function, and capacity to proliferate in vivo. To further understand the factors that contribute to the differential homeostasis of NP/MP subsets, we examined the differential effects of CD28 and CTLA-4 interaction with CD80/CD86, as well as MHC class II-TCR interaction within mouse Treg pools and CD4+ and CD8+ T cell pools. Blockade of CD80/CD86 with CTLA-4-Ig markedly reduced the cycling and absolute numbers of MP Tregs and MP CD4+ T cells, with minimal effect on the NP T cell subpopulations. Blockade of MHC class II-TCR interaction led to selective expansion of MP Tregs and MP CD4+ and CD8+ T cells that was reversed upon cotreatment with CTLA-4-Ig. Treatment with anti-CTLA-4 mAb altered MP Treg and MP CD4+ and CD8+ T cell homeostasis in a manner similar to that observed with anti-MHC class II. We postulate a complex pathway in which CD28 is the primary driver of Treg proliferation and CTLA-4 functions as the main brake but is likely dependent on TCR signals and CD80/CD86. These findings have important implications for the use of biologic agents targeting such pathways to modulate autoimmune and neoplastic disease.

Mortality and cancer incidence among female Australian firefighters.

OBJECTIVES: To investigate the mortality and cancer incidence of female firefighters, a group where there are limited published findings. METHODS: Participating fire agencies supplied records of individual firefighters including the number and type of incidents attended. The cohort was linked to the Australian National Death Index and Australian Cancer Database. Standardised mortality ratios and standardised cancer incidence ratios were calculated separately for paid and volunteer firefighters. Volunteer firefighters were grouped into tertiles by the duration of service and by a number of incidents attended and relative mortality ratios and relative incidence ratios calculated. RESULTS: For volunteer firefighters (n=37 962), the overall risk of mortality and risk from all major causes of death were reduced when compared with the general population whether or not they had ever attended incidents. Volunteer firefighters had a similar cancer incidence when compared with the general population for most major cancer categories. Female volunteer firefighters have usually attended few fires. Of those who had turned out to incidents, only one-third had attended more than 12 fires about half the number for male volunteers. Mortality and cancer incidence for paid female firefighters (n=1682) were similar to the general population but the numbers were small and so power was limited. CONCLUSIONS: Female volunteer firefighters have a cancer incidence similar to the general population but a reduced risk of mortality which is likely to be a result of a 'healthy volunteer' effect.Most of the paid female firefighters were relatively recent recruits and it will be important to monitor the health of this group as more women are recruited to front-line firefighting roles.

Exposure to noise and ototoxic chemicals in the Australian workforce.

OBJECTIVE: To determine the current prevalence of exposure to workplace noise and ototoxic chemicals, including co-exposures. METHOD: A cross-sectional telephone survey of nearly 5000 Australian workers was conducted using the web-based application, OccIDEAS. Participants were asked about workplace tasks they performed and predefined algorithms automatically assessed worker's likelihood of exposure to 10 known ototoxic chemicals as well as estimated their full shift noise exposure level (LAeq,8h) of their most recent working day. Results were extrapolated to represent the Australian working population using a raked weighting technique. RESULTS: In the Australian workforce, 19.5% of men and 2.8% of women exceeded the recommended full shift noise limit of 85 dBA during their last working day. Men were more likely to be exposed to noise if they were younger, had trade qualifications and did not live in a major city. Men were more likely exposed to workplace ototoxic chemicals (57.3%) than women (25.3%). Over 80% of workers who exceeded the full shift noise limit were also exposed to at least one ototoxic chemical in their workplace. CONCLUSION: The results demonstrate that exposures to hazardous noise and ototoxic chemicals are widespread in Australian workplaces and co-exposure is common. Occupational exposure occurs predominantly for men and could explain some of the discrepancies in hearing loss prevalence between genders.

Night shift work and breast cancer: a pooled analysis of population-based case-control studies with complete work history.

Night shift work has been suspected to increase breast cancer risk but epidemiological studies have been inconsistent due to heterogeneous assessment of exposure to night work. To overcome this limitation, we pooled data of five population-based case-control studies from Australia, Canada, France, Germany, and Spain into a single harmonized dataset using a common definition of night work including 6093 breast cancer cases and 6933 population controls. The odds ratio for breast cancer in women who ever worked at night for at least 3 h between midnight and 5 a.m. as compared to never night workers was 1.12 (95% CI 1.00-1.25). Among pre-menopausal women, this odds ratio was 1.26 [1.06-1.51], increasing to 1.36 [1.07-1.74] for night shifts ≥ 10 h, 1.80 [1.20-2.71] for work ≥ 3 nights/week, and 2.55 [1.03-6.30] for both duration of night work ≥ 10 years and exposure intensity ≥ 3 nights/week. Breast cancer risk in pre-menopausal women was higher in current or recent night workers (OR = 1.41 [1.06-1.88]) than in those who had stopped night work more than 2 years ago. Breast cancer in post-menopausal women was not associated with night work whatever the exposure metric. The increase in risk was restricted to ER+ tumors, particularly those who were both ER+ and HER2+ . These results support the hypothesis that night shift work increases the risk of breast cancer in pre-menopausal women, particularly those with high intensity and long duration of exposure. Risk difference between pre- and post-menopausal women deserves further scrutiny.

Shift work that involves circadian disruption and breast cancer: a first application of chronobiological theory and the consequent challenges.

OBJECTIVES: In 2007, the International Agency for Research on Cancer classified shift work involving circadian disruption (CD) as probably carcinogenic to humans. Circadian disruption could be conceptualised as the overlap of activity, such as work, with an individual's biological night. The latter can be approximated from a worker's chronotype (or morning/evening preference). Few previous studies have taken chronotype into account when assessing CD caused by shift work. Our objective was to test the hypothesis that women working during their biological night would be at increased risk of breast cancer. METHODS: We used data from our case-control study of breast cancer to investigate associations between shift work involving CD and breast cancer risks. Previously, we had assumed that everyone working in jobs which involved work for two or more shifts between midnight and 05:00 hours was equally exposed to CD. In the present analyses, we reclassified as unexposed those who had a late chronotype in which their preferred bedtime was 2 hours after the end of their shift. RESULTS: Only 30 of 1385 night jobs changed classification and the overall finding (OR 1.17, 95% CI 0.98 to 1.41) was not different to the original finding when chronotype was not considered. CONCLUSIONS: We found virtually no difference between our new and old classifications of exposure. However, we were not able to calculate the total number of chronodisrupted shifts over a lifetime in order to assess dose and nor were we able to determine how many women were exposed to CD when doing shifts which began before midnight. Our first practical application highlights challenges for future chronobiology-based research.

Prevalence of occupational exposure to asthmagens derived from animals, fish and/or shellfish among Australian workers.

OBJECTIVE: Several animal, fish and/or shellfish derived substances encountered in the workplace can initiate or exacerbate asthma. The aims of this study were: to produce a population-based estimate of the current prevalence of occupational exposure to animal, fish and/or shellfish derived asthmagens, to identify the main circumstances of exposures and to identify occupations with the highest proportions of exposed respondents. METHODS: We used data from the Australian Work Exposure Study-Asthma, a national telephone survey that investigated the current prevalence of occupational exposure to asthmagens among Australian workers. A web-based tool was used to collect job task information and assign exposure to asthmagens, including animal, fish and/or shellfish derived asthmagens. Prevalence ratios to determine risk factors for exposure were estimated using modified Poisson regression. RESULTS: Of the 4878 respondents, 12.4% were exposed to asthmagens derived from animals, fish and/or shellfish. Exposure to these asthmagens was significantly higher in workers residing in regional and remote areas, compared with major cities. The main circumstance of exposure to animal derived asthmagens was through cleaning up rat/mice infestations, while the main circumstance of exposure to fish and/or shellfish derived asthmagens was through preparing and cooking salmon. Occupational groups with the highest proportion of exposure to animal or fish and/or shellfish derived asthmagens were farmers/animal workers and food workers, respectively. CONCLUSIONS: This is the first study investigating occupational exposure to animal, fish and/or shellfish derived asthmagens in a nationwide working population. The results of this study can be used to inform the direction of occupational interventions and policies to reduce work-related asthma.