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Particulate matter (PM) containing environmentally persistent free radicals (EPFR) is formed by the incomplete combustion of organic wastes, resulting in the chemisorption of pollutants to the surface of PM containing redox-active transition metals. In prior studies in mice, EPFR inhalation impaired endothelium-dependent vasodilation. These findings were associated with aryl hydrocarbon receptor (AhR) activation in the alveolar type-II (AT-II) cells that form the air-blood interface in the lung. We thus hypothesized that AhR activation in AT-II cells promotes the systemic release of mediators that promote endothelium dysfunction peripheral to the lung. To test our hypothesis, we knocked down AhR in AT-II cells of male and female mice and exposed them to 280 µg/m3 EPFR lo (2.7e + 16 radicals/g) or EPFR (5.5e + 17 radicals/g) compared with filtered air for 4 h/day for 1 day or 5 days. AT-II-AhR activation-induced EPFR-mediated endothelial dysfunction, reducing endothelium-dependent vasorelaxation by 59%, and eNOS expression by 50%. It also increased endothelin-1 mRNA levels in the lungs and peptide levels in the plasma in a paracrine fashion, along with soluble vascular cell adhesion molecule-1 and iNOS mRNA expression, possibly via NF-kB activation. Finally, AhR-dependent increases in antioxidant response signaling, coupled to increased levels of 3-nitrotyrosine in the lungs of EPFR-exposed littermate control but not AT-II AhR KO mice suggested that ATII-specific AhR activation promotes oxidative and nitrative stress. Thus, AhR activation at the air-blood interface mediates endothelial dysfunction observed peripheral to the lung, potentially via release of systemic mediators. [ABSTRACT FROM AUTHOR]

ObjectiveA double-blind, randomized controlled trial showed that low-dose glucocorticoid therapy in pediatric ARDS patients is feasible and may improve both ventilation and oxygenation indices in these patients. However, the molecular mechanisms underlying potential changes in outcomes remain unclear. Based on these clinical findings, this study was designed to examine the effects of intravenous methylprednisolone on circulating inflammatory biomarkers in pediatric ARDS patients.DesignDouble-blind, placebo-controlled randomized trial with blood collection on study entry and day 7.SettingTertiary care children's hospital.PatientsChildren (0-18years) with ARDS undergoing mechanical ventilation.Interventions35 children were randomized within 72h of mechanical ventilation. The glucocorticoid group received methylprednisolone 2mg/kg loading dose followed by 1mg/kg/day continuous infusion from days 1 to 7. Both groups were ventilated following the ARDSnet recommendations. WBC and differential cell counts, plasma cytokines and CRP levels, and coagulation parameters were analyzed on days 0 and 7.ResultsAt study entry, the placebo group had higher IL-15 and basophil levels. On day 7, in comparison to study entry, the placebo group had lower IL-1α, IFN-γ and IL-10 levels. The glucocorticoid group had lower INF-α, IL-6, IL-10, MCP-1, G-CSF and GM-CSF levels, and higher IL-17α levels on day 7 in comparison to study entry. Total and differential cell counts remained unchanged within the placebo group between days 0 and 7, whereas in the glucocorticoid group total WBC and platelets counts were increased on day 7. Pearson's correlation studies within the placebo and glucocorticoid groups revealed positive and negative correlations between cytokine levels, cell counts, coagulation parameters and relevant clinical parameters of disease severity identified in our previous study. Multiple regression models identified several cytokines as predictors for alterations in clinical parameters of disease severity.ConclusionThis pilot study shows the feasibility of simultaneously measuring multiple inflammatory cytokines, cell counts and coagulation parameters in pediatric ARDS patients. We report statistical models that may be useful for future, larger trials to predict ARDS severity and outcomes.

ObjectiveLung injury activates multiple pro-inflammatory pathways, including neutrophils, epithelial, and endothelial injury, and coagulation factors leading to acute respiratory distress syndrome (ARDS). Low-dose methylprednisolone therapy (MPT) improved oxygenation and ventilation in early pediatric ARDS without altering duration of mechanical ventilation or mortality. We evaluated the effects of MPT on biomarkers of endothelial [Ang-2 and soluble intercellular adhesion molecule-1 (sICAM-1)] or epithelial [soluble receptor for activated glycation end products (sRAGE)] injury, neutrophil activation [matrix metalloproteinase-8 (MMP-8)], and coagulation (plasminogen activator inhibitor-1).DesignDouble-blind, placebo-controlled randomized trial.SettingTertiary-care pediatric intensive care unit (ICU).PatientsMechanically ventilated children (0-18 years) with early ARDS.InterventionsBlood samples were collected on days 0 (before MPT), 7, and 14 during low-dose MPT (n = 17) vs. placebo (n = 18) therapy. The MPT group received a 2-mg/kg loading dose followed by 1 mg/kg/day continuous infusions from days 1 to 7, tapered off over 7 days; placebo group received equivalent amounts of 0.9% saline. We analyzed plasma samples using a multiplex assay for five biomarkers of ARDS. Multiple regression models were constructed to predict associations between changes in biomarkers and the clinical outcomes reported earlier, including P/F ratio on days 8 and 9, plateau pressure on days 1 and 2, PaCO2 on days 2 and 3, racemic epinephrine following extubation, and supplemental oxygen at ICU discharge.ResultsNo differences occurred in biomarker concentrations between the groups on day 0. On day 7, reduction in MMP-8 levels (p = 0.0016) occurred in the MPT group, whereas increases in sICAM-1 levels (p = 0.0005) occurred in the placebo group (no increases in sICAM-1 in the MPT group). sRAGE levels decreased in both MPT and placebo groups (p

This letter discusses two pilot feasibility studies that examined the impact of smoke exposure on lung health. The first study focused on wildfire smoke exposure during a prescribed fire in Brisbane, Australia. It found that particulate matter levels were significantly higher during the burn period and that children's lung function showed abnormalities. The second study looked at the health effects of wood-fired stove smoke exposure using particulate filters as a model. It found that PM2.5 levels increased near the filters, suggesting potential adverse impacts on lung health. The study recommends further investigation into public health advice regarding indoor exposure during wood-fired stove events and calls for more research on indoor air quality under transient smoke conditions. [Extracted from the article]

Hepatitis E virus (HEV) is a single-stranded RNA virus in the family Hepeviridae (1). HEV is transmitted through the fecal-oral and bloodborne routes and typically causes transient hepatitis; however, such [...]