Asbestos in combination with tobacco smoke exposure reportedly leads to more severe physiological consequences than asbestos alone; limited data also show an increased disease risk due to environmental tobacco smoke (ETS) exposure. Environmental influences during gestation and early lung development can result in physiological changes that alter risk for disease development throughout an individual's lifetime. Therefore, maternal lifestyle may impact the ability of offspring to subsequently respond to environmental insults and alter overall disease susceptibility. In this study, we examined the effects of exposure to ETS in utero and during early postnatal development on asbestos-related inflammation and disease in adulthood. ETS exposure in utero appeared to shift inflammation towards a Th2 phenotype, via suppression of Th1 inflammatory cytokine production. This effect was further pronounced in mice exposed to ETS in utero and during early postnatal development. In utero ETS exposure led to increased collagen deposition, a marker of fibrotic disease, when the offspring was later exposed to asbestos, which was further increased with additional ETS exposure during early postnatal development. These data suggest that ETS exposure in utero alters the immune responses and leads to greater disease development after asbestos exposure, which is further exacerbated when exposure to ETS continues during early postnatal development.

Prenatal and early-life environmental tobacco smoke (ETS) exposure can induce epigenetic alterations associated with inflammation and respiratory disease. The objective of this study was to address the long-term epigenetic consequences of perinatal ETS exposure on latent respiratory disease risk, which are still largely unknown. C57BL/6 mice were exposed to prenatal and early-life ETS; offspring lung pathology, global DNA, and gene-specific methylation were measured at two adult ages. Significant alterations in global DNA methylation and promoter methylation of IFN-γ and Thy-1 were found in ETS-exposed offspring at 10-12 and 20 weeks of age. These sustained epigenetic alterations preceded the onset of significant pulmonary pathologies observed at 20 weeks of age. This study suggests that perinatal ETS exposure induces persistent epigenetic alterations in global DNA, as well as IFN-γ and Thy-1 promoter methylation that precede the adult onset of fibrotic lung pathology. These epigenetic findings could represent potential biomarkers of latent respiratory disease risk.