The effect of nanoparticles on pulmonary fibrosis: a systematic review and Meta-analysis of preclinical studies

Abstract Air pollution is a big ecumenical problem associated with public health around the world. The rapid development of nanotechnology worldwide resulted in a significant increase in human exposure with unknown particles, and ultimately leading to an increase in acute and chronic diseases. The effect of nanoparticles on pulmonary fibrosis has been reported in vivo and in vitro studies; however, the results are inconsistent. The present systematic review and meta-analysis of animal preclinical studies was conducted to assess the effect of nanoparticles on pulmonary fibrosis. A systematic search of online databases and gray literature as well as reference lists of retrieved studies was performed up to February 2019 to identify preclinical animal studies. Studies were assessed for methodological quality using the SYstematic Review Center for Laboratory animal Experimentation bias risk tool (SYRCLE's ROB tool). Pooled standardized mean difference (SMD) estimate with corresponding 95% CI was calculated using inverse-variance weights method while random effects meta-analysis was used, taking into account conceptual heterogeneity. To assess the robustness of pooled estimates as well as heterogeneity across studies, sensitivity analysis and Cochran Q statistic (with I2 statistic) was carried out using Stata 11.0. Of 6494 retrieved studies, 85 were reviewed in depth for eligibility. 16 studies met the criteria for inclusion in this systematic review. The meta-analysis was conducted on 10 studies which had reported the mean of TGF-β in 7 days after exposure by nanoparticles jointly (exposure compared to no exposure). Findings showed that exposure to nanoparticles significantly induced pulmonary fibrosis (SMD: 4.12, 95% CI: 2.57-5.67). A statistical heterogeneity was found [P < 0.001 (Q statistics), I 2 = 83.0%] across studies. Nanoparticles were the most influencing in inducing pulmonary fibrosis in animal models. Sensitivity analysis demonstrated consistency of the results, indicating that the meta-analysis model was robust. Publication bias (using visual inspection and statistical tests) was unlikely in the association between nanoparticles and pulmonary fibrosis. We found that the nanoparticles significantly induce pulmonary fibrosis through increasing proinflammatory cytokine TGF-β and histopathological changes.