Use of multi-walled carbon nanotubes (MWCNT) is growing which increases occupational exposures to these materials. Their toxic potential makes it important to have an in-depth understanding of the inflammation and disease that develops due to exposure. Epigenetics is one area of interest that has been quickly developing to assess disease processes due to its ability to change gene expression and thus the lung environment after exposure. In this study, promoter methylation of inflammatory genes (IFN-γ and TNF-α) was measured after MWCNT exposure using the pyrosequencing assay and found to correlate with initial cytokine production. In addition, methylation of a gene involved in tissue fibrosis (Thy-1) was also altered in a way that matched collagen deposition. In addition to using epigenetics to better understand disease processes, it has also been used as a biomarker of exposure and disease. In this study, global methylation was determined in the lung to ascertain whether MWCNT alter global methylation at the site of exposure and if those alterations coincide with disease development. Then, global methylation levels were determined in the blood to ascertain whether global methylation could be used as a biomarker of exposure in a more easily accessible tissue. Using the LuUminometric Methylation Assay (LUMA) and 5-Methylcytosine (5-mC) Quantification assay, we found that MWCNT lead to DNA hypomethylation in the lung and blood, which coincided with disease development. This study provides initial data showing that alterations in gene-specific methylation correspond with an inflammatory response to MWCNT exposure. In addition, global DNA methylation in the lung and blood coincides with MWCNT-induced disease development, suggesting its potential as a biomarker of both exposure and disease development.

OBJECTIVE:We implemented 5 potentially better practices to limit mechanical ventilation (MV), supplemental oxygen, and bronchopulmonary dysplasia in newborn infants born before 33 weeks' gestation. METHODS:The methods used in this study included (1) exclusive use of bubble continuous positive airway pressure (bCPAP), (2) provision of bCPAP in the delivery room, (3) strict intubation criteria, (4) strict extubation criteria, and (5) prolonged CPAP to avoid supplemental oxygen. We excluded outborn infants and those with major anomalies and obstetric complications from analysis. RESULTS:Demographics were similar in 61 infants born before and 60 born after implementation. For infants born at 26 to 32 6 ⁄ 7 weeks' gestation, intubation (first 72 hours) decreased from 52% to 11% (P Ͻ .0001) and surfactant use decreased from 48% to 14% (P ϭ .0001). In all infants, the mean Ϯ SD fraction of inspired oxygen requirement (first 24 hours) decreased from 0.27 Ϯ 0.08 to 0.24 Ϯ 0.05 (P ϭ .0005), days of oxygen decreased from 23.5 Ϯ 44.5 to 9.3 Ϯ 22.0 (P ϭ .04), and days of MV decreased from 8.8 Ϯ 27.8 to 2.2 Ϯ 6.2 (P ϭ .005). Hypotension decreased from 33% to 15% (P ϭ .03). The percentage of infants with bronchopulmonary dysplasia was 17% before and 8% after (P ϭ .27). Nurse staffing ratios remained unchanged. CONCLUSIONS:Implementation of these potentially better practices reduced the need for MV, surfactant, and supplemental oxygen as well as reduced hypotension among infants born before 33 weeks' gestation without adverse consequences. The costs for equipment and surfactant were lower. Pediatrics 2011;128:e218-e226 All the authors made substantive intellectual contributions to this report. Dr Levesque contributed to the conception and design of the study, implementation, data collection, analysis, and interpretation, drafted the article, and approved the version submitted; Dr Kalish contributed to the data analysis and interpretation and critical revising of the article for important intellectual content and approved the final version submitted; and Ms LaPierre, Ms Welch, and Ms Porter participated in the conception and design, implementation, data collection and interpretation, and revising of the article and approved the version submitted.www.pediatrics.org/cgi

Epidemiological studies have shown a correlation between chronic biomass smoke exposure and increased respiratory infection. Pulmonary macrophages are instrumental in both the innate and the adaptive immune responses to respiratory infection. In the present study, in vitro systems were utilized where alveolar macrophages (AM) and bone marrow-derived macrophages (BMdM) were exposed to concentrated wood smoke-derived particulate matter (WS-PM) and mice were exposed in vivo to either concentrated WS-PM or inhaled WS. In vivo studies demonstrated that WS-exposed mice inoculated with Streptococcus pneumoniae had a higher bacterial load 24 h post-exposure, and corresponding AM were found to have decreased lymphocyte activation activity. Additionally, while classic markers of inflammation (cellular infiltration, total protein, neutrophils) were not affected, there were changes in pulmonary macrophages populations, including significant decreases in macrophages expressing markers of activation in WS-exposed mice. The lymphocyte activation activity of WS-PM-exposed AM was significantly suppressed, but the phagocytic activity appeared unchanged. In an effort to determine a pathway for WS-induced suppression, RelB activation, assessed by nuclear translocation, was observed in AM exposed to either inhaled WS or instilled WS-PM. Finally, an analysis of WS-PM fractions determined the presence of 4–5 polycyclic aromatic hydrocarbons (PAHs), and preliminary work suggests a potential role for these PAHs to alter macrophage functions. These studies show a decreased ability of WS-exposed pulmonary macrophages to effectively mount a defense against infection, the effect lasts at least a week post-exposure, and appears to be mediated via RelB activation.