American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Dec 2014
Relationship of DNA Methylation and Gene Expression in Idiopathic Pulmonary Fibrosis (IPF).
Idiopathic pulmonary fibrosis (IPF) is an untreatable and often fatal lung disease that is increasing in prevalence and is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control gene expression and are likely to regulate the IPF transcriptome. ⋯ These results suggest that DNA methylation may be involved in the pathogenesis of IPF.
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Am. J. Respir. Crit. Care Med. · Dec 2014
Clinical Predictors of the Respiratory Arousal Threshold in Patients with Obstructive Sleep Apnea.
A low respiratory arousal threshold (ArTH) is one of several traits involved in obstructive sleep apnea pathogenesis and may be a therapeutic target; however, there is no simple way to identify patients without invasive measurements. ⋯ Our results demonstrate that individuals with a low ArTH can be identified from standard, clinically available variables. This finding could facilitate larger interventional studies targeting the ArTH.
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Am. J. Respir. Crit. Care Med. · Dec 2014
Sustained Effects of Sirolimus on Lung Function and Cystic Lung Lesions in Lymphangioleiomyomatosis.
Sirolimus therapy stabilizes lung function and reduces the size of chylous effusions and lymphangioleiomyomas in patients with lymphangioleiomyomatosis. ⋯ Sirolimus therapy slowed down lung function decline and increase in cystic lesions. Most patients were able to tolerate sirolimus therapy.
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Am. J. Respir. Crit. Care Med. · Dec 2014
α-1 Antitrypsin Activates Protein Phosphatase 2A (PP2A) to Counter Lung Inflammatory Responses.
α1-Antitrypsin (A1AT) was identified as a plasma protease inhibitor; however, it is now recognized as a multifunctional protein that modulates immunity, inflammation, proteostasis, apoptosis, and cellular senescence. Like A1AT, protein phosphatase 2A (PP2A), a major serine-threonine phosphatase, regulates similar biologic processes and plays a key role in chronic obstructive pulmonary disease. ⋯ Together, these data indicate that A1AT modulates PP2A to counter inflammatory and proteolytic responses induced by TNF signaling in the lung.
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Am. J. Respir. Crit. Care Med. · Dec 2014
RBCs Induce Necroptosis of Lung Endothelial Cells and Increase Susceptibility to Lung Inflammation.
Red blood cell (RBC) transfusions are associated with increased risk of acute respiratory distress syndrome (ARDS) in the critically ill, yet the mechanisms for enhanced susceptibility to ARDS conferred by RBC transfusions remain unknown. ⋯ RBC transfusion enhances susceptibility to lung inflammation through release of HMGB1 and induces necroptosis of lung EC. Necroptosis and subsequent danger signal release is a novel mechanism of injury following transfusion that may account for the increased risk of ARDS in critically ill transfused patients.