American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Oct 2019
Long-Term Exposure to Ozone and Cause-Specific Mortality Risk in the United States.
Rationale: Many studies have linked short-term exposure to ozone (O3) with morbidity and mortality, but epidemiologic evidence of associations between long-term O3 exposure and mortality is more limited. Objectives: To investigate associations of long-term (annual or warm season average of daily 8-h maximum concentrations) O3 exposure with all-cause and cause-specific mortality in the NIH-AARP Diet and Health Study, a large prospective cohort of U. S. adults with 17 years of follow-up from 1995 to 2011. ⋯ The results were robust to alternative models and adjustment for copollutants (fine particulate matter and nitrogen dioxide), although some evidence of confounding by temperature was observed. Significantly elevated respiratory disease mortality risk associated with long-term O3 exposure was found among those living in locations with high temperature (Pinteraction < 0.05). Conclusions: This study found that long-term exposure to O3 is associated with increased risk for multiple causes of mortality, suggesting that establishment of annual and/or seasonal federal O3 standards is needed to more adequately protect public health from ambient O3 exposures.
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Am. J. Respir. Crit. Care Med. · Oct 2019
Multicenter StudyMulticenter Preclinical Validation of BET Inhibition for the Treatment of Pulmonary Arterial Hypertension.
Rationale: Pulmonary arterial hypertension (PAH) is a degenerative arteriopathy that leads to right ventricular (RV) failure. BRD4 (bromodomain-containing protein 4), a member of the BET (bromodomain and extra-terminal motif) family, has been identified as a critical epigenetic driver for cardiovascular diseases. Objectives: To explore the therapeutic potential in PAH of RVX208, a clinically available BET inhibitor. ⋯ This reversed the PAH phenotype in isolated PAH microvascular endothelial cells and smooth muscle cells in vitro, and in diverse PAH rat models. RVX208 also supported the pressure-loaded RV in vivo. Together, these data support the establishment of a clinical trial with RVX208 in patients with PAH.