Description: Objectives Noise-induced hearing loss is one of the most serious occupational diseases worldwide. It is caused by interactions between environmental and genetic factors. The purpose of this study was to examine the association between the genetic susceptibility of the eye absent homolog 4 (EYA4) gene and the risk of developing noise-induced hearing loss in China. Methods A case–control association study was carried out with 326 hearing loss cases and 326 controls matched with age and duration of noise exposure, drawn from a cohort of steel workers. Five single nucleotide polymorphisms (SNPs) in the EYA4 were selected and genotyped. Logistic regression was performed to analyse the main effect of genotypes and interactions between genotypes and individual/environmental factors adjusted for confounding factors. Moreover, generalised multiple dimensionality reduction was applied to further detect interaction among the 5 selected SNPs. Results Analysis revealed that locus polymorphism of rs3813346 was associated with the risk of developing noise-induced hearing loss in the dominance model, the codominance model and the addictive model (p=0.004, 0.009 and 0.003, respectively). A significant interaction between rs9321402 and cumulative noise exposure was found (p=0.002). A significant main effect p value (p=0.006) was obtained in the high-level exposure group (cumulative noise exposure ≥98 dB(A)). Generalised multiple dimensionality reduction indicated that the combined interaction of the 2 loci—rs3813346 and rs9493627—significantly affected the incidence of noise-induced hearing loss. Conclusions The research suggests that EYA4 genetic variant and its interaction with noise levels may modify the susceptibility to develop noise-induced hearing loss in Chinese population.

Description: Objectives There is evidence of adverse associations between short-term exposure to traffic-related pollution and health, but little is known about the relative contribution of the various sources and particulate constituents. Methods For each day for 2011–2012 in London, UK over 100 air pollutant metrics were assembled using monitors, modelling and chemical analyses. We selected a priori metrics indicative of traffic sources: general traffic, petrol exhaust, diesel exhaust and non-exhaust (mineral dust, brake and tyre wear). Using Poisson regression models, controlling for time-varying confounders, we derived effect estimates for cardiovascular and respiratory hospital admissions at prespecified lags and evaluated the sensitivity of estimates to multipollutant modelling and effect modification by season. Results For single day exposure, we found consistent associations between adult (15–64 years) cardiovascular and paediatric (0–14 years) respiratory admissions with elemental and black carbon (EC/BC), ranging from 0.56% to 1.65% increase per IQR change, and to a lesser degree with carbon monoxide (CO) and aluminium (Al). The average of past 7 days EC/BC exposure was associated with elderly (65+ years) cardiovascular admissions. Indicated associations were higher during the warm period of the year. Although effect estimates were sensitive to the adjustment for other pollutants they remained consistent in direction, indicating independence of associations from different sources, especially between diesel and petrol engines, as well as mineral dust. Conclusions Our results suggest that exhaust related pollutants are associated with increased numbers of adult cardiovascular and paediatric respiratory hospitalisations. More extensive monitoring in urban centres is required to further elucidate the associations.

Description: Background To date, the association of the neurotoxic agent cadmium (Cd) with depression in elderly people has been poorly evaluated. By investigating the relationship between blood cadmium levels and scores on a depression screening test, we aimed to investigate the impact of cadmium exposure on elderly depression. Methods From 2008 to 2010, a total of 395 elderly participants residing in Seoul, Korea, were evaluated 3 times. Demographic data and lifestyle information were obtained via a systemised questionnaire, and blood samples were collected for analysis. Participants underwent the Korean Version of the Short Form Generic Depression Scale test (SGDS-K) for screening depression and associations were estimated using logistic regression models adjusted for potential confounders. Results Blood cadmium levels were associated with depressive symptoms in the first visit data analysis. By analysing the first visit data, the highest quartile blood cadmium group (Q4) showed increased risk for depressive symptoms compared to the lowest quartile group (Q1) (OR 3.50, 95% CI 1.22 to 10.00). However, the data of the second and third visits suggested that blood cadmium may be protective against depressive symptoms (second visit data, Q4 vs Q1, OR 0.78, 95% CI 0.19 to 3.14; third visit data, Q4 vs Q1, OR 0.58, 95% CI 0.04 to 8.77). Conclusions Owing to inconsistent results in analyses between blood cadmium levels and depressive symptoms, we cannot conclude any solid association between blood cadmium levels and depressive symptoms in the elderly population. To clarify the relationship, other prospective studies are needed in the future.

Description: Background Welders are at risk for cardiovascular disease. Recent studies linked tobacco smoke exposure to hypomethylation of the F2RL3 (coagulation factor II (thrombin) receptor-like 3) gene, a marker for cardiovascular disease prognosis and mortality. However, whether welding fumes cause hypomethylation of F2RL3 remains unknown. Methods We investigated 101 welders (median span of working as a welder: 7 years) and 127 unexposed controls (non-welders with no obvious exposure to respirable dust at work), age range 23–60 years, all currently non-smoking, in Sweden. The participants were interviewed about their work history, lifestyle factors and diseases. Personal sampling of respirable dust was performed for the welders. DNA methylation of F2RL3 in blood was assessed by pyrosequencing of four CpG sites, CpG_2 (corresponds to cg03636183) to CpG_5, in F2RL3 . Multivariable linear regression analysis was used to assess the association between exposure to welding fumes and F2RL3 methylation. Results Welders had 2.6% lower methylation of CpG_5 than controls (p〈0.001). Higher concentrations of measured respirable dust among the welders were associated with hypomethylation of CpG_2, CpG_4 and CpG_5 (β=–0.49 to –1.4, p〈0.012); p〈0.029 adjusted for age, previous smoking, passive smoking, education, current residence and respirator use. Increasing the number of years working as a welder was associated with hypomethylation of CpG_4 (linear regression analysis, β=–0.11, p=0.039, adjusted for previous smoking). Previous tobacco smokers had 1.5–4.7% (p〈0.014) lower methylation of 3 of the 4 CpG sites in F2RL3 (CpG_2, CpG_4 and CpG_5) compared to never-smokers. A non-significant lower risk of cardiovascular disease with more methylation was observed for all CpG sites. Conclusions Welding fumes exposure and previous smoking were associated with F2RL3 hypomethylation. This finding links low-to-moderate exposure to welding fumes to adverse effects on the cardiovascular system, and suggests a potential mechanistic pathway for this link, via epigenetic effects on F2RL3 expression.

Description: Objectives To conduct a systematic review of changes in lung function in relation to presence of pleural plaques in asbestos-exposed populations. Methods Database searches of PubMed and Web of Science were supplemented by review of papers’ reference lists and journals’ tables of contents. Methodological features (eg, consideration of potential confounding by smoking) of identified articles were reviewed by ≥two reviewers. Meta-analyses of 20 studies estimated a summary effect of the decrements in per cent predicted (%pred) forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV 1 ) associated with presence of pleural plaques. Results Among asbestos-exposed workers, the presence of pleural plaques was associated with statistically significant decrements in FVC (4.09%pred, 95% CI 2.31 to 5.86) and FEV 1 (1.99%pred, 95% CI 0.22 to 3.77). Effects of similar magnitude were seen when stratifying by imaging type (X-ray or high-resolution CT) and when excluding studies with potential methodological limitations. Undetected asbestosis was considered as an unlikely explanation of the observed decrements. Several studies provided evidence of an association between size of pleural plaques and degree of pulmonary decrease, and presence of pleural plaques and increased rate or degree of pulmonary impairment. Conclusions The presence of pleural plaques is associated with a small, but statistically significant mean difference in FVC and FEV 1 in comparison to asbestos-exposed individuals without plaques or other abnormalities. From a public health perspective, small group mean decrements in lung function coupled with an increased rate of decline in lung function of the exposed population may be consequential.

Description: Objective To compare short-term effects of fine particles (PM 2.5 ; aerodynamic diameter 〈2.5 µm) from different sources on the blood levels of markers of systemic inflammation. Methods We followed a panel of 52 ischaemic heart disease patients from 15 November 2005 to 21 April 2006 with clinic visits in every second week in the city of Kotka, Finland, and determined nine inflammatory markers from blood samples. In addition, we monitored outdoor air pollution at a fixed site during the study period and conducted a source apportionment of PM 2.5 using the Environmental Protection Agency's model EPA PMF 3.0. We then analysed associations between levels of source-specific PM 2.5 and markers of systemic inflammation using linear mixed models. Results We identified five source categories: regional and long-range transport (LRT), traffic, biomass combustion, sea salt, and pulp industry. We found most evidence for the relation of air pollution and inflammation in LRT, traffic and biomass combustion; the most relevant inflammation markers were C-reactive protein, interleukin-12 and myeloperoxidase. Sea salt was not positively associated with any of the inflammatory markers. Conclusions Results suggest that PM 2.5 from several sources, such as biomass combustion and traffic, are promoters of systemic inflammation, a risk factor for cardiovascular diseases.

Description: Objective Occupationally acquired noise-induced hearing loss (NIHL) is the most prevalent occupational disease in Austria and among the most common in many other countries. Because of the wide variation in hearing loss after equivalent exposures it has long been assumed that some individuals are more vulnerable to occupational NIHL than others. Earlier attempts to define predictors of NIHL before starting occupational noise exposure have largely failed. We present results of a prospective study evaluating the potential of temporary threshold shift (TTS) after a test exposure to predict NIHL. Methods Between 1982 and 1989, overall 311 apprentices were included into a prospective study during their initial health screening visit. At this occasion, a standardised noise exposure was applied (20 min, 200–500 Hz, 100 dBA) and the TTS at 4 kHz was determined during at least 10 min after exposure. Hearing loss was monitored at follow-up visits every 3–5 years. Follow-up was 13 years on average. Results Permanent threshold shift was predicted by duration of noise exposure, frequency of wearing noise protectors and especially by the initial TTS at 4 kHz. Using 14 dB TTS as a cut-off had 82% sensitivity and 53% specificity to predict 20 dB or higher levels of NIHL. Conclusions The TTS model can be successfully applied as a method to detect individuals at greater risk of occupational NIHL. It is recommended to routinely include such a procedure into initial workers’ examinations for suitability to work under occupational noise conditions and for counselling on the use of hearing protectors.

Description: Objective The study was designed to investigate whether beryllium exposure was related to illness diagnosed as sarcoidosis. Chronic beryllium disease (CBD) and sarcoidosis are clinically and pathologically indistinguishable, with only the presence of beryllium-specific T-lymphocytes identifying CBD. Testing for such cells is not feasible in community studies of sarcoidosis but a second characteristic of CBD, its much greater incidence in those with a glutamic acid residue at position 69 of the HLA-DPB1 gene (Glu69), provides an alternative approach to answering this question. Methods Cases of sarcoidosis aged 18–60 years diagnosed in Alberta, Canada, from 1999 to 2005 were approached through their specialist physician, together with age-matched and sex-matched referents with other chronic lung disease. Referents were grouped into chronic obstructive pulmonary disease (COPD), asthma and other lung disease. Participants completed a telephone questionnaire, including industry-specific questionnaires. DNA was extracted from mailed-in mouthwash samples and genotyped for Glu69. Duration of employment in types of work with independently documented beryllium exposure was calculated. Results DNA was extracted for 655 cases (270 Glu69 positive) and 1382 referents (561 positive). No increase in sarcoidosis was seen with either Glu69 or beryllium exposure (none, 〈10, ≥10 years) as main effects: longer duration in possible beryllium jobs was related to COPD. In Glu69 positive men with exposure ≥10 years, the trend towards increasing rate of COPD was reversed, and a significant interaction of duration of exposure and Glu69 was detected (OR=4.51 95% CI 1.17 to 17.48). Conclusions The gene–environment interaction supports the hypothesis that some cases diagnosed as sarcoidosis result from occupational beryllium exposure.

Description: Objectives The role of outdoor air pollution in the incidence of chronic obstructive pulmonary disease (COPD) remains unclear. We investigated this question using a large, nationally representative cohort based on primary care records linked to hospital admissions. Methods A cohort of 812 063 patients aged 40–89 years registered with 205 English general practices in 2002 without a COPD diagnosis was followed from 2003 to 2007. First COPD diagnoses recorded either by a general practitioner (GP) or on admission to hospital were identified. Annual average concentrations in 2002 for particulate matter with an aerodynamic diameter 〈10 µm (PM 10 ) and 〈2.5 µm (PM 2.5 ), nitrogen dioxide (NO 2 ), ozone and sulfur dioxide (SO 2 ) at 1 km 2 resolution were estimated from emission-based dispersion models. Hazard ratios (HRs) per interquartile range change were estimated from Cox models adjusting for age, sex, smoking, body mass index and area-level deprivation. Results 16 034 participants (1.92%) received a COPD diagnosis from their GP and 2910 participants (0.35%) were admitted to hospital for COPD. After adjustment, HRs for GP recorded COPD and PM 10 , PM 2.5 and NO 2 were close to unity, positive for SO 2 (HR=1.07 (95% CI 1.03 to 1.11) per 2.2 µg/m 3 ) and negative for ozone (HR=0.94 (0.89 to 1.00) per 3 µg/m 3 ). For admissions HRs for PM 2.5 and NO 2 remained positive (HRs=1.05 (0.98 to 1.13) and 1.06 (0.98 to 1.15) per 1.9 µg/m 3 and 10.7 µg/m 3 , respectively). Conclusions This large population-based cohort study found limited, inconclusive evidence for associations between air pollution and COPD incidence. Further work, utilising improved estimates of air pollution over time and enhanced socioeconomic indicators, is required to clarify the association between air pollution and COPD incidence.

Description: Objectives To investigate inter-reader agreement for the detection of pleural and parenchymal abnormalities using CT in a large cross-sectional study comprising information on individual cumulative exposure to asbestos. Methods The project was approved by the hospital ethics committee, and all patients received information on the study and gave their written informed consent. In 5511 CT scans performed in a cohort of retired workers previously exposed to asbestos and volunteering to participate in a multiregional survey programme (Asbestos Related Diseases Cohort, ARDCO), double randomised standardised readings, triple in case of disagreement, were performed by seven trained expert radiologists specialised in thoracic imaging and blind to the initial interpretation. Inter-reader agreement was evaluated by calculating the -weighted coefficient between pairs of expert readers and results of routine practice and final diagnosis after expert reading. Results -Weighted coefficients between trained experts ranged from 0.28 to 0.52 (fair to good), 0.59 to 0.86 (good to excellent) and 0.11 to 0.66 (poor to good) for the diagnosis of asbestosis, pleural plaques and fibrosis of the visceral pleura, respectively. -Weighted coefficients between results of routine practice and final diagnosis after expert reading were 0.13 (poor), 0.53 (moderate) and 0.11 (poor) for the diagnosis of asbestosis, pleural plaques and fibrosis of the visceral pleura, respectively. Conclusions Interpretation of benign asbestos-related thoracic abnormalities requires standardisation of the reading and trained readers, particularly for participants asking for compensation, and with a view to the longitudinal survey of asbestos-exposed workers.