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ObjectivesIncreased risks of rheumatoid arthritis, small vessel vasculitis, systemic lupus erythematosus, and systemic sclerosis have been observed following crystalline silica exposure. Our aims are to estimate pooled risk estimates and assess the impact of study quality.MethodsWe followed the PRISMA criteria, identified 1162 articles, and included 21 studies that we classified according to eight quality parameters (high vs. low). We estimated pooled overall and disease specific odds ratios (ORs) with random effects meta-regressions.ResultsWe observed an increased overall OR of 2.3 (1.7–3.1, 21 studies) and for rheumatoid arthritis (OR 1.7, 95% CI 0.8–3.41, 6 studies), small vessel vasculitis (OR 2.4, 95% CI 1.2–4.7, 6 studies), systemic lupus erythematosus (OR 2.8, 95% CI 0.5–14.7, 3 studies), and systemic sclerosis (OR) 2.9, 1.7–4.9, 6 studies). The following high-quality characteristics were associated with decreased ORs: appropriate control group, high response rate, appropriate confounder control, independent exposure information, and many participants; and with increased ORs: quantitative or semi-quantitative exposure measure, hospital based diagnosis, and well-defined diagnostic criteria. Only the latter was statistically significant (p<0.05). When we consecutively excluded low quality studies, the overall OR value decreased to 1.3 (0.4–4.2, 3 studies) but this exercise was sensitive to the order. Egger’s test of no small study effect was highly statistically significant (p<0.01).ConclusionThis review provides some evidence that crystalline silica is associated with systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and small vessel vasculitis. However, more high-quality studies are needed to confirm or refute if this represents causal associations.

Phagocytosis is thought to be the most important internalization pathway for single-walled carbon nanotubes (SWCNTs) with a length of 1 μm or more and thus for SWCNT related toxicity. In this paper we therefore focused on the effect of SWCNT exposure on cytotoxicity, cell cycle, gene expression and cytokine release in the non-phagocytic A549 lung epithelial cell line and phagocytic human monocyte derived THP-1 and mouse J774 macrophages. The J774 cell line was found to be the most efficient at taking up SWCNTs and its phagocytic ability was 4 times higher than for THP-1. The effect of SWCNT exposure on the different cell lines significantly increased with their ability to take up SWCNTs (J774 > THP-1 > A549). In contrast to A549 and THP-1, exposure to 10 μg mL−1SWCNTs affected all the investigated parameters in J774 and led to, e.g., changed cell morphology, reduced cell viability, induction of necrosis, reduced phagocytic ability, increased ROS levels, induction of regulation of gene expression and cytokine release. In contrast, apoptosis was not induced. Our results strongly suggest that the toxic effects of SWCNTs are linked to the phagocytic activity of cells and suggest that there might be a difference in how human and mouse macrophages react to SWCNT exposure.