Search

Inhalation of crystalline silica (CS) can cause silicosis, which is one of the most serious interstitial lung diseases worldwide. Autophagy dysfunction is an essential step in silicosis progression. In this study, we aim to identify the effect of growth arrest‐specific protein 6 (Gas6) during autophagy induction and macrophage inflammatory response caused by CS. After RAW 264.7 macrophages exposed to CS, the levels of Gas6 and autophagy markers (p62, Beclin1, and LC3‐II/LC3‐I) were increased, accompanied with enhanced inflammatory cytokines secretion. Using autophagy activator (rapamycin) repressed, whereas autophagy inhibitor (3‐methyladenine) promoted inflammatory cytokines release. Besides, inhibition of Gas6 aggravated CS‐induced inflammatory response, and autophagy inhibition facilitated the promoted effect of Gas6 silencing, resulting in elevated expression of inflammatory cytokines. These findings reveal the protective effects of Gas6 and autophagy in macrophages in response to CS exposure, and highlight the autophagy regulated by Gas6 may be a potential prevention target for CS‐induced lung inflammatory response. [ABSTRACT FROM AUTHOR]

Background: Little is known about the different risk of silicosis in metal mines and pottery factories. We aimed to compare the silicosis risks among silica-exposed workers in different industrial circumstances.Research Question: Are the silicosis risks among silica-exposed workers in industrial circumstances different?Study Design and Methods: We studied 39,808 workers followed up from January 1, 1960 to December 31, 2003 in China. Cumulative respirable silica dust exposure (CDE) was estimated by linking a job-exposure matrix to personal work history. Silicosis of stage I or higher was diagnosed by Chinese pneumoconiosis Roentgen diagnostic criteria.Results: A total of 9,377 silicosis patients were diagnosed during 1,153,580.9 person-years' follow-up in the cohort. Hazard ratios of silicosis for each 1 mg/m3-year increase in CDE were 1.08 (1.07-1.08) for tungsten mines, 1.41 (1.33-1.48) for iron and copper mines, 1.14 (1.11-1.17) for tin mines, and 1.03 (1.02-1.04) for pottery factories, respectively. When exposed to 0.05 mg/m3 of respirable silica dust for 45 years, the cumulative risks in metal mines (2.3%, 9.9%, 1.5% for tungsten mines, iron and copper mines, and tin mines, respectively) were still higher than those in pottery factories (0.6%). The joint effect of silica and smoking on silicosis was more than multiplicative.Interpretation: The risk of silicosis in metal miners is higher than that in pottery workers when exposed to the same level of silica dust. The silica dust exposed years should be under 10 years for metal miners and 40 years for pottery workers at 0.05 mg/m3 to keep lifetime risk within 0.1%. Current exposure limits should take into account differences in various industrial circumstances. Smoking cessation could help reduce silicosis risk for silica-exposed workers. [ABSTRACT FROM AUTHOR]

Crystalline silica has been classified as a human carcinogen by the International Agency for Research on Cancer (Lyon, France); however, few previous studies have provided quantitative data on silica exposure, silicosis, and/or smoking. We investigated a cohort in China (in 1960–2003) of 34,018 workers without exposure to carcinogenic confounders. Cumulative silica exposure was estimated by linking a job-exposure matrix to work history. Cox proportional hazards model was used to conduct exposure-response analysis and risk assessment. During a mean 34.5-year follow-up, 546 lung cancer deaths were identified. Categorical analyses by quartiles of cumulative silica exposure (using a 25-year lag) yielded hazard ratios of 1.26, 1.54, 1.68, and 1.70, respectively, compared with the unexposed group. Monotonic exposure-response trends were observed among nonsilicotics (P for trend < 0.001). Analyses using splines showed similar trends. The joint effect of silica and smoking was more than additive and close to multiplicative. For workers exposed from ages 20 to 65 years at 0.1 mg/m3 of silica exposure, the estimated excess lifetime risk (through age 75 years) was 0.51%. These findings confirm silica as a human carcinogen and suggest that current exposure limits in many countries might be insufficient to protect workers from lung cancer. They also indicate that smoking cessation could help reduce lung cancer risk for silica-exposed individuals. [ABSTRACT FROM PUBLISHER]

Background. The detailed lung radiographic response to silica exposure has not been described. In estimating the exposure-response relationship in silicosis with statistical models, the absence of baseline (unattributable) risk can disable relative-rate estimation or produce widely varying estimates. This obstructs identification of optimum exposure metrics and invalidates comparisons and meta-analyses, which assume a common background rate. Methods. A cohort of 3,000 Chinese tin miners with more than 1,000 cases of silicosis was analyzed for the period 1961-1994. Regular surveillance documented three stages of silicosis. To examine the exposure-response relationship, the intercept in relative-rate models was fixed to correspond to 1% of the observed silicosis rate. Exposure metrics for contributions in different time-windows were simultaneously evaluated, as were burden and cumulative burden metrics. Results. Silica exposures that most contributed to silicosis onset occurred in the period 5-10 years prior (excess annual rate per 10 mg-year/m3, ER = 0.158, 95% CI = 0.125-0.192, or 16% per year). During 10-20 year prior, the excess rate contribution was much smaller (ER = 0.048, 95% CI = 0.037-0.060) but larger again during 20-30 year prior to onset (ER = 0.112, 95% CI = 0.098-0.126). For advanced silicosis, all time periods contributed about equally to the rate of onset. Conclusions. Reliable estimates of parameters were observed, demonstrating exposure contributions over time. Burden metrics with different half-lives suggested some reversibility for silicosis onset with a half-life of 20 years. Advanced silicosis was best predicted with a cumulative burden metric which was consistent with prior observations that previously deposited silica continues to cause pulmonary damage. Am. J. Ind. Med. 56:267-275, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The role of silica in the causation of lung cancer is an ongoing debate. In order to explore whether observed association between silica exposure and lung cancer is confounded by exposure to other occupational carcinogens, we updated a previously nested case-control study among a cohort of male workers in 29 Chinese mines and factories on the basis of an extended follow-up. Five hundred and eleven lung cancer cases and 1,879 matched controls were selected. Exposure to respirable silica as well as relevant occupational confounders were quantitatively assessed based on historical industrial hygiene data. The relationship between exposure to silica and lung cancer was analyzed by conditional logistic regression analysis adjusted for exposure to arsenic, polycyclic aromatic hydrocarbons (PAHs), radon, and smoking. In a crude analysis adjusted for smoking only, a significant trend of increasing risk of lung cancer with exposure to silica was found for tin, iron/copper miners, and pottery workers. But after adjustment for relevant occupational confounders, no relationship between silica and lung cancer can be observed. Instead, there is a significant association between lung cancer mortality and cumulative exposure to inorganic arsenic (OR = 1.86, 95% CI: 1.14, 3.04 for each mg/m3-year increase) and carcinogenic PAHs (OR = 1.35, 95% CI: 1.08, 1.69 for each 100 μg/m3-year increase). This analysis does not provide any evidence to show that exposure to silica causes lung cancer in the absence of confounding factors. [ABSTRACT FROM AUTHOR]

Background: Crystalline silica is considered as one of the most common and serious occupational hazards to workers' health. Although its association with lung cancer has been studied for many decades, the conclusion remains somewhat controversial. Our objectives are to review and summarize the epidemiological evidence on the relationship between occupational silica exposure and risk of lung cancer and to provide an update on this major occupational health concern.Methods: Eligible studies up to 29 April 2016 were identified. Pooled effect estimates were calculated according to the reported outcome and the study design. Cohort, case control and proportional mortality studies were examined separately. Studies reporting results according to silicotic status were grouped together and analyzed. Due to the significant amount of heterogeneity expected, random effects models were implemented. Subgroup and meta-regression analyses (both univariate and multivariate) were performed in an attempt to explain heterogeneity. Studies which had adequate exposure characterization were selected to find out whether there was an exposure-response relationship between silica and lung cancer.Results: The risk of lung cancer was found to be elevated in both silicotics and non-silicotics. The pooled standardized mortality ratio (SMR) was 2.32 with a 95 % confidence interval (95 % CI) of 1.91-2.81 and 1.78 (95 % CI 1.07-2.96) respectively. The pooled standardized incidence ratio (SIR) was 2.49 (95 % CI 1.87-3.33) and 1.18 (95 % CI 0.86-1.62) respectively. Subgroup analysis showed that workers in the mining industry had the highest risk of lung cancer with a pooled SMR of 1.48 (95 % CI 1.18-1.86) and the weakest association was seen in potteries with a pooled SMR of 1.14 (95 % CI 1.05-1.23). A positive exposure-response relation was found between cumulative silica exposure and risk of lung cancer.Conclusion: The results of our meta-analysis supported the carcinogenic role of silica on the lungs, which was more pronounced at higher levels of exposure, in the presence of silicosis and in the mining industry. Further research is needed to evaluate whether non-silicotics are truly at risk, whether a predisposing factor would explain this potential risk, and to determine the mechanism of carcinogenicity of silica in humans. [ABSTRACT FROM AUTHOR]

This study aims to develop a prognostic risk prediction model for the development of silicosis among workers exposed to silica dust in China. The prediction model was performed by using retrospective cohort of 3,492 workers exposed to silica in an iron ore, with 33 years of follow-up. We developed a risk score system using a linear combination of the predictors weighted by the LASSO penalized Cox regression coefficients. The model's predictive accuracy was evaluated using time-dependent ROC curves. Six predictors were selected into the final prediction model (age at entry of the cohort, mean concentration of respirable silica, net years of dust exposure, smoking, illiteracy, and no. of jobs). We classified workers into three risk groups according to the quartile (Q1, Q3) of risk score; 203 (23.28%) incident silicosis cases were derived from the high risk group (risk score ≥ 5.91), whilst only 4 (0.46%) cases were from the low risk group (risk score < 3.97). The score system was regarded as accurate given the range of AUCs (83-96%). This study developed a unique score system with a good internal validity, which provides scientific guidance to the clinicians to identify high-risk workers, thus has important cost efficient implications. [ABSTRACT FROM AUTHOR]

Environmental exposure to crystalline silica particles can lead to silicosis, which is one of the most serious pulmonary interstitial fibrosis around the world. Unfortunately, the exact mechanism on silicosis is unclear, and the effective treatments are lacking to date. In this study, we aim to explore the molecular mechanism by which interleukin-11 (IL-11) affects silica particles-induced lung inflammation and fibrosis. We observed that IL-11 expressions in mouse lungs were significantly increased after silica exposure, and maintained at high levels across both inflammation and fibrosis phase. Immunofluorescent dual staining further revealed that the overexpression of IL-11 mainly located in mouse lung epithelial cells and fibroblasts. Using neutralizing anti-IL-11 antibody could effectively alleviate the overexpression of pro-inflammatory cytokines (i.e., interleukin-6 and tumor necrosis factor-α) and fibrotic proteins (i.e., collagen type I and matrix metalloproteinase-2) induced by silica particles. Most importantly, the expressions of IL-11 receptor subunit α (IL-11Rα), Glycoprotein 130 (GP130), and phosphorylated extracellular signal-regulated kinase (p-ERK) were significantly increased in response to silica, whereas blocking of IL-11 markedly reduced their levels. All findings suggested that the overexpression of IL-11 was involved in the pathological of silicosis, while neutralizing IL-11 antibody could effectively alleviate the silica-induced lung inflammation and fibrosis by inhibiting the IL-11Rα/GP130/ERK signaling pathway. IL-11 might be a promising therapeutic target for lung inflammation and fibrosis caused by silica particles exposure. [Display omitted] [ABSTRACT FROM AUTHOR]

Silica particles are commonly encountered in natural and industrial activities. Long-term environmental exposure to silica can result in silicosis, which is characterized by chronic inflammation and abnormal tissue repair in lung. To uncover the role of m6A modification in silica-induced pulmonary inflammation, we conducted this study using established mouse and macrophage models. In this study, the aerodynamic diameter of silica particles was approximately 1–2 µm. We demonstrated that silica exposure in mice caused pulmonary inflammation and increased global m6A modification levels, the downregulation of alkB homolog 5 (ALKBH5) might contribute to this alteration. Besides, we found that F4/80, a macrophage-specific biomarker, was co-expressed with ALKBH5 through dual immunofluorescent staining. In vitro studies using MeRIP assays suggested that Slamf7 was a target gene regulated by m6A modification, and specific inhibition of ALKBH5 increased Slamf7 expression. Mechanistically, ALKBH5 promoted m6A modification of Slamf7, which decreased Slamf7 mRNA stability in an m6A-dependent manner, ultimately regulating Slamf7 expression. In addition, silica exposure activated PI3K/AKT and induced macrophage autophagy. Inhibition of Slamf7 promoted autophagy, reduced the secretion of pro-inflammatory cytokines, and improved silica-induced pulmonary inflammation. In summary, ALKBH5 can regulate silica-induced pulmonary inflammation by modulating Slamf7 m6A modification and affecting the function of macrophage autophagy. [Display omitted] • Silica-caused pulmonary inflammation was accompanied by increased m6A modification. • ALKBH5 regulated the alteration of m6A modification induced by silica exposure. • Slamf7 was a target gene in silica-induced inflammation modulated by ALKBH5. • Macrophage autophagy regulated by Slamf7 was associated with pulmonary inflammation. [ABSTRACT FROM AUTHOR]

Genetic loss of Gas6 or Mer alleviated autophagosomes accumulation via reducing its formation and promoting the degradation. • Silica induced autophagosomes and prevented its degradation in mice lung tissues. • Gas6 or Mer deficiency attenuated the silica-induced accumulation of autophagosomes. • Gas6 affected the expression of Mer receptor in the development of silicosis. Published evidences have shown that autophagy plays an important role in silica-induced lung inflammation and collagen deposition. Our previous study found that the level of growth arrest-specific protein 6 (Gas6) in bronchoalveolar lavage fluid was increased after silica exposure. However, it is unclear whether Gas6 is involved in the regulation of silica-induced autophagy dysfunction. In this study, we observed an autophagosomes accumulation in wild-type C57BL/6 (WT) mice lung after silica intratracheal instillation and then investigated whether genetic loss of Gas6 (Gas6−/−) could ameliorate it. Our data showed that Gas6−/− mice exhibited a limited autophagosomes accumulation from days 7–84 after silica exposure, revealed by reduced induction and increased degradation of autophagosomes in mice lung tissue. Interestingly, silica particles could elevate the expression of Mer receptor, which was significantly decreased in Gas6−/− mice (P < 0.05). Furthermore, we found that Mer deficiency (Mer−/−) could also reduce the formation of autophagosomes and restore the function of impaired lysosomes in silica-treated mice. Taken together, our results indicate that genetic loss of Gas6 attenuates silica-induced autophagosomes accumulation partly through down-regulating the expression of Mer receptor. Targeting Gas6/Mer-mediated autophagy pathway may provide a novel insight into the prevention and therapy of silica-induced pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

• High-Mobility Group Box 1 (HMGB-1) was elevated after exposure to silica. • HMGB-1 participate in silica-induced pulmonary inflammatory response and fibrosis. • HMGB-1 participate in pathogenesis of silicosis partly via regulating EMT process. • Inhibition of HMGB-1 attenuates inflammation and fibrosis by regulating EMT. Silicosis is an inflammatory and fibrotic lung disease caused by prolonged inhalation of silica. The potential role of high-mobility group box-1 (HMGB-1) and its underlying mechanisms in silicosis remain unclear. In this study, intratracheal instillation of a silica suspension was used to establish silicosis in male C57BL/6 mice. To elucidate the effects of HMGB-1 on the pathogenesis of silicosis, we used HMGB-1 neutralizing antibody (anti-HMGB-1) and recombinant HMGB-1 (rmHMGB-1) to abrogate or increase the HMGB-1 levels, respectively. At days 7, 28, and 84, the accumulation of macrophages and neutrophils decreased by anti-HMGB-1 treatment. The expression levels of interleukin-6 and tumor necrosis factor-α in lung increased in response to silica exposure across three time points; anti-HMGB-1 could alleviate those expressions at day 28 and 84. In contrast, rmHMGB-1 aggravated this process. At days 28 and 84, the protein expression of fibronectin and col1a1 decreased in the silica + anti-HMGB-1 groups but increased in silica + rmHMGB-1 groups compared to mice with silica alone. Further study suggested that HMGB-1-mediated epithelial-mesenchymal transition participated in the development of silicosis. In conclusion, the findings demonstrate that HMGB-1 participates in the pathogenesis of silicosis and may represent a potential therapeutic target for the treatment of silicosis. [ABSTRACT FROM AUTHOR]

• Gas6 level in BALF elevated persistently from day 7 to 84 in silica-treated mice. • Gas6 or Mer deficiency limited the silica-induced pulmonary inflammation. • Gas6 or Mer deficient mice exhibited an alleviated pulmonary fibrosis. Long-term inhalation of crystalline silica particles leads to silicosis characterized by pulmonary inflammation and interstitial fibrosis. The growth arrest-specific protein 6 (Gas6) and its tyrosine receptor Mer have been implicated to involve in the regulation of inflammation, innate immunity and tissue repair. However, the role of Gas6 or Mer in silica-induced lung inflammation and fibrosis has not been investigated previously. In this study, we observed a remarkable increase of Gas6 in bronchoalveolar lavage fluid (BALF) from wild-type C57BL/6 mice after silica intratracheal administration. Then, we investigated whether genetic loss of Gas6 or Mer could attenuate silica-induced lung inflammation and fibrosis. Our results showed that Gas6−/− and Mer−/− mice exhibited reduced lung inflammation response from days 7 to 84 after silica exposure. We also uncovered an overexpression of the suppressor of cytokine signaling protein 1 in silica-treated deficient mice. Moreover, Gas6 or Mer deficiency attenuated silica-induced collagen deposition by inhibiting the expression of transforming growth factor-β. We conclude that gene absence of Gas6 or Mer is protective against silica-induced lung inflammation and fibrosis in mice. Targeting Gas6/Mer pathway may be a potential therapeutic approach to treat pulmonary fibrosis in patients with silicosis. [ABSTRACT FROM AUTHOR]

Pharmacological targeting of MARCO with polyG (MARCO inhibitor) attenuated the silica-induced fibrosis through suppressing the ERS-associated apoptosis and inhibiting the EMT process. • ERS was involved in silica-induced pulmonary fibrosis. • Therapeutic administration of polyG alleviated silica-induced pulmonary fibrosis in rats. • Antagonism of scavenger receptor MARCO reduced ERS-related apoptosis and EMT in silica-exposed rats. Pulmonary fibrosis induced by prolonged exposure to silica particles is a chronic and irreversible lung disease without effective treatment till now. Our previous study has shown that early intervention with MARCO antagonist PolyG could alleviate pulmonary fibrosis in silica-exposed rats. However, the therapeutic effects of PolyG on silica-induced pulmonary fibrosis have rarely been reported. In this study, we explored the effects of administration (on the 28th day after silica exposure) of PolyG (MARCO inhibitor) on an established rat silicosis model. The lungs were analyzed histopathologically in rats using HE and Masson staining. The silica-induced ERS-related apoptosis, EMT and fibrosis were evaluated using western blotting, qRT-PCR and immunohistochemical analyses. The results suggested that silica exposure could increase the MARCO activity, and induce ERS and EMT in lung tissues. Pharmacological targeting of MARCO with PolyG attenuated the development of pulmonary fibrosis in silica-exposed rats. Further study indicated that PolyG could inhibit silica-induced ERS-related apoptosis and EMT process. Together, our findings reveal an essential function of ERS-related apoptosis and EMT in the processes of pulmonary fibrosis caused by silica, and identify MARCO as a potential therapeutic pharmacological target for silicosis. [ABSTRACT FROM AUTHOR]

Abstract Background The World Health Organization (WHO) and the International Labour Organization (ILO) are developing a joint methodology for estimating the national and global work-related burden of disease and injury (WHO/ILO joint methodology), with contributions from a large network of experts. In this paper, we present the protocol for two systematic reviews of parameters for estimating the number of deaths and disability-adjusted life years attributable to pneumoconiosis from occupational exposure to dusts and/or fibres, to inform the development of the WHO/ILO joint methodology. Objectives We aim to systematically review studies on occupational exposure to dusts and/or fibres (Systematic Review 1) and systematically review and meta-analyse estimates of the effect of occupational exposure to dusts and/or fibres on pneumoconiosis (Systematic Review 2), applying the Navigation Guide systematic review methodology as an organizing framework. Data sources Separately for Systematic Reviews 1 and 2, we will search electronic academic databases for potentially relevant records from published and unpublished studies, including Medline, EMBASE, Web of Science and CISDOC. We will also search electronic grey literature databases, Internet search engines and organizational websites; hand-search reference list of previous systematic reviews and included study records; and consult additional experts. Study eligibility and criteria We will include working-age (≥15 years) study participants in the formal and informal economy in any WHO and/or ILO Member State but exclude children (<15 years) and unpaid domestic workers. Eligible risk factors will be dusts and/or fibres from: (i) asbestos; (ii) silica; and/or (iii) coal (defined as pure coal dust and/or dust from coal mining). Included outcomes will be (i) asbestosis; (ii) silicosis; (iii) coal worker pneumoconiosis; and (iv) unspecified pneumoconiosis. For Systematic Review 1, we will include quantitative prevalence studies of occupational exposure to dusts and/or fibres (i.e. no versus any exposure) stratified by country, sex, age and industrial sector or occupation. For Systematic Review 2, we will include randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies with an estimate of any occupational exposure to dusts and/or fibres on the prevalence of, incidence of or mortality due to pneumoconiosis, compared with the theoretical minimum risk exposure level of no exposure. Study appraisal and synthesis methods At least two review authors will independently screen titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. At least two review authors will assess risk of bias and the quality of evidence, using the most suited tools currently available. For Systematic Review 2, if feasible, we will combine relative risks using meta-analysis. We will report results using the guidelines for accurate and transparent health estimates reporting (GATHER) for Systematic Review 1 and the preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA) for Systematic Review 2. PROSPERO registration number CRD42018084131. Highlights • A protocol was prepared for two systematic reviews in the field of occupational health. • Principles of the Navigation Guide systematic review methodology were applied. • The protocol detailed instructions how to assess the quality of selected studies. [ABSTRACT FROM AUTHOR]

[Display omitted] The World Health Organization (WHO) and the International Labour Organization (ILO) are developing joint estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large number of individual experts. Evidence from human, animal and mechanistic data suggests that occupational exposure to dusts and/or fibres (silica, asbestos and coal dust) causes pneumoconiosis. In this paper, we present a systematic review and meta -analysis of the prevalences and levels of occupational exposure to silica, asbestos and coal dust. These estimates of prevalences and levels will serve as input data for estimating (if feasible) the number of deaths and disability-adjusted life years that are attributable to occupational exposure to silica, asbestos and coal dust, for the development of the WHO/ILO Joint Estimates. We aimed to systematically review and meta -analyse estimates of the prevalences and levels of occupational exposure to silica, asbestos and coal dust among working-age (≥ 15 years) workers. We searched electronic academic databases for potentially relevant records from published and unpublished studies, including Ovid Medline, PubMed, EMBASE, and CISDOC. We also searched electronic grey literature databases, Internet search engines and organizational websites; hand-searched reference lists of previous systematic reviews and included study records; and consulted additional experts. We included working-age (≥ 15 years) workers in the formal and informal economy in any WHO and/or ILO Member State but excluded children (< 15 years) and unpaid domestic workers. We included all study types with objective dust or fibre measurements, published between 1960 and 2018, that directly or indirectly reported an estimate of the prevalence and/or level of occupational exposure to silica, asbestos and/or coal dust. At least two review authors independently screened titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, then data were extracted from qualifying studies. We combined prevalence estimates by industrial sector (ISIC-4 2-digit level with additional merging within Mining, Manufacturing and Construction) using random-effects meta -analysis. Two or more review authors assessed the risk of bias and all available authors assessed the quality of evidence, using the ROB-SPEO tool and QoE-SPEO approach developed specifically for the WHO/ILO Joint Estimates. Eighty-eight studies (82 cross-sectional studies and 6 longitudinal studies) met the inclusion criteria, comprising > 2.4 million measurements covering 23 countries from all WHO regions (Africa, Americas, Eastern Mediterranean, South-East Asia, Europe, and Western Pacific). The target population in all 88 included studies was from major ISCO groups 3 (Technicians and Associate Professionals), 6 (Skilled Agricultural, Forestry and Fishery Workers), 7 (Craft and Related Trades Workers), 8 (Plant and Machine Operators and Assemblers), and 9 (Elementary Occupations), hereafter called manual workers. Most studies were performed in Construction, Manufacturing and Mining. For occupational exposure to silica, 65 studies (61 cross-sectional studies and 4 longitudinal studies) were included with > 2.3 million measurements collected in 22 countries in all six WHO regions. For occupational exposure to asbestos, 18 studies (17 cross-sectional studies and 1 longitudinal) were included with > 20,000 measurements collected in eight countries in five WHO regions (no data for Africa). For occupational exposure to coal dust, eight studies (all cross-sectional) were included comprising > 100,000 samples in six countries in five WHO regions (no data for Eastern Mediterranean). Occupational exposure to silica, asbestos and coal dust was assessed with personal or stationary active filter sampling; for silica and asbestos, gravimetric assessment was followed by technical analysis. Risk of bias profiles varied between the bodies of evidence looking at asbestos, silica and coal dust, as well as between industrial sectors. However, risk of bias was generally highest for the domain of selection of participants into the studies. The largest bodies of evidence for silica related to the industrial sectors of Construction (ISIC 41–43), Manufacturing (ISIC 20, 23–25, 27, 31–32) and Mining (ISIC 05, 07, 08). For Construction, the pooled prevalence estimate was 0.89 (95% CI 0.84 to 0.93, 17 studies, I2 91%, moderate quality of evidence) and the level estimate was rated as of very low quality of evidence. For Manufacturing, the pooled prevalence estimate was 0.85 (95% CI 0.78 to 0.91, 24 studies, I2 100%, moderate quality of evidence) and the pooled level estimate was rated as of very low quality of evidence. The pooled prevalence estimate for Mining was 0.75 (95% CI 0.68 to 0.82, 20 studies, I2 100%, moderate quality of evidence) and the pooled level estimate was 0.04 mg/m3 (95% CI 0.03 to 0.05, 17 studies, I2 100%, low quality of evidence). Smaller bodies of evidence were identified for Crop and animal production (ISIC 01; very low quality of evidence for both prevalence and level); Professional, scientific and technical activities (ISIC 71, 74; very low quality of evidence for both prevalence and level); and Electricity, gas, steam and air conditioning supply (ISIC 35; very low quality of evidence for both prevalence and level). For asbestos, the pooled prevalence estimate for Construction (ISIC 41, 43, 45,) was 0.77 (95% CI 0.65 to 0.87, six studies, I2 99%, low quality of evidence) and the level estimate was rated as of very low quality of evidence. For Manufacturing (ISIC 13, 23–24, 29–30), the pooled prevalence and level estimates were rated as being of very low quality of evidence. Smaller bodies of evidence were identified for Other mining and quarrying (ISIC 08; very low quality of evidence for both prevalence and level); Electricity, gas, steam and air conditioning supply (ISIC 35; very low quality of evidence for both prevalence and level); and Water supply, sewerage, waste management and remediation (ISIC 37; very low quality of evidence for levels). For coal dust, the pooled prevalence estimate for Mining of coal and lignite (ISIC 05), was 1.00 (95% CI 1.00 to 1.00, six studies, I2 16%, moderate quality of evidence) and the pooled level estimate was 0.77 mg/m3 (95% CI 0.68 to 0.86, three studies, I2 100%, low quality of evidence). A small body of evidence was identified for Electricity, gas, steam and air conditioning supply (ISIC 35); with very low quality of evidence for prevalence, and the pooled level estimate being 0.60 mg/m3 (95% CI −6.95 to 8.14, one study, low quality of evidence). Overall, we judged the bodies of evidence for occupational exposure to silica to vary by industrial sector between very low and moderate quality of evidence for prevalence, and very low and low for level. For occupational exposure to asbestos, the bodies of evidence varied by industrial sector between very low and low quality of evidence for prevalence and were of very low quality of evidence for level. For occupational exposure to coal dust, the bodies of evidence were of very low or moderate quality of evidence for prevalence, and low for level. None of the included studies were population-based studies (i.e., covered the entire workers' population in the industrial sector), which we judged to present serious concern for indirectness, except for occupational exposure to coal dust within the industrial sector of mining of coal and lignite. Selected estimates of the prevalences and levels of occupational exposure to silica by industrial sector are considered suitable as input data for the WHO/ILO Joint Estimates, and selected estimates of the prevalences and levels of occupational exposure to asbestos and coal dust may perhaps also be suitable for estimation purposes. Protocol identifier: https://doi.org/10.1016/j.envint.2018.06.005. PROSPERO registration number: CRD42018084131. [ABSTRACT FROM AUTHOR]

The main characteristic of silicosis is irreversible fibrosis. Certain studies have shown that epithelial–mesenchymal transition (EMT) regulated by transforming growth factor-β (TGF-β) is involved in fibrosis. Thus, we suggest that TGF-β regulated EMT may play an important role in silicosis. In this study, we determined the expression of TGF-β-Smad2/3, EMT- and ECM-related markers in lung epithelial cells treated with silica particle by RT-PCR, western-blot and ELISA. In order to explore the role of TGF-β, we used TGF-β inhibitor in the cell model. We found that the cells lost the expression of epithelial phenotypic markers and acquired increased expression of mesenchymal cells markers with ECM deposition after treatment with silica particle. Moreover, the changes of EMT-related event was restricted in response to TGF-β inhibitor. These findings suggest that EMT is essentially involved in the pathogenesis of fibrosis induced by silica particles and down-regulating the TGF-β expression can inhibit the process of EMT. [ABSTRACT FROM AUTHOR]

To investigate the regulated role of IL-1β in initiating and maintaining inflammation, PMA-differentiated THP-1 macrophages were exposed to two micro-sized crystalline silica particles (Si3–5 μm and Si1 μm) from 3 h to 24 h, respectively. Cytotoxicity and inflammatory cytokines (IL-1β, TNF-α and IL-6) expressions measured showed that they were induced by both silica particles in positive dose-dependent manners. The levels of inflammatory cytokines induced by Si1 μm were higher than those induced by Si3–5 μm at low concentration. When pretreated with anti-human IL-1β, not only the high levels of IL-1β but also elevated TNF-α and IL-6 induced by both silica particles were remarkably blocked, especially Si1 μm particle. In addition, recombinant human IL-1β protein could induce macrophages to strikingly augment TNF-α and IL-6 expressions. Our data suggest that IL-1β could play a critical role of switching regulation in the downstream inflammation induced by micro-sized silica particles. [ABSTRACT FROM AUTHOR]

The association of silica dust exposure with mortality among never smokers has not been well established. We aimed to evaluate the association of silica dust exposure with mortality among never smokers. We studied 17,130 workers employed for at least 1 year between January 1, 1960 and December 31, 1974, with follow-up until the end of 2013. Cumulative respirable silica dust exposure (CDE) was estimated by linking a job-exposure matrix to personal work history. We observed 3937 deaths during 589,357.26 person-years of follow-up. Significant positive exposure-response relationships were found between CDE and mortality from all cause (HR = 1.01, 95%CI = 1.01-1.02), respiratory tuberculosis (HR = 1.04, 95%CI = 1.02-1.06), CVDs (HR = 1.03, 95%CI = 1.02-1.04), and diseases of the respiratory system (HR = 1.06, 95%CI = 1.04-1.07). We found higher standardized mortality ratios for respiratory tuberculosis (2.62, 2.32-2.95), CVDs (1.43, 1.32-1.54), and pneumoconiosis (77.75, 68.21-88.25) among silica dust exposed workers. In addition, we estimated that 4.19%, 20.69%, 7.48% and 34.06% of deaths for all cause, respiratory tuberculosis, CVDs, and diseases of the respiratory system among Chinese workers were attributed to silica, after adjusting for other covariates. With regard to lung cancer, compared with unexposed group, the HRs and 95% CI were 0.94 (0.52-1.71), 1.86 (1.15-3.00), 1.65 (0.95-2.86) for low, medium, and high exposed workers, respectively. Long-term silica dust exposure is associated with increased mortality in the absence of cigarette smoking. [ABSTRACT FROM AUTHOR]