American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Nov 2016
Circulating Plasma Extracellular Microvesicle miRNA Cargo and Endothelial Dysfunction in OSA Children.
Obese children are at increased risk for developing obstructive sleep apnea (OSA), and both of these conditions are associated with an increased risk for endothelial dysfunction (ED) in children, an early risk factor for atherosclerosis and cardiovascular disease. Although weight loss and treatment of OSA by adenotonsillectomy improve endothelial function, not every obese child or child with OSA develops ED. Exosomes are circulating extracellular vesicles containing functional mRNA and microRNA (miRNA) that can be delivered to other cells, such as endothelial cells. ⋯ These observations elucidate a novel role of exosomal miRNA-360 as a putative key mediator of vascular function and cardiovascular disease risk in children with underlying OSA and/or obesity, and identify therapeutic targets.
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Am. J. Respir. Crit. Care Med. · Nov 2016
Observational StudyNasopharyngeal Microbiota, Host Transcriptome and Disease Severity in Children with Respiratory Syncytial Virus Infection.
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity, especially among healthy children. We postulate that the severity of RSV infection is influenced by modulation of the host immune response by the local bacterial ecosystem. ⋯ Our data suggest that interactions between RSV and nasopharyngeal microbiota might modulate the host immune response, potentially affecting clinical disease severity.
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Am. J. Respir. Crit. Care Med. · Nov 2016
Systems Biology and Clinical Practice in Respiratory Medicine: The Twain Shall Meet.
Respiratory diseases are highly complex, being driven by host-environment interactions and manifested by inflammatory, structural, and functional abnormalities that vary over time. Traditional reductionist approaches have contributed vastly to our knowledge of biological systems in health and disease to date; however, they are insufficient to provide an understanding of the behavior of the system as a whole. In this Pulmonary Perspective, we discuss systems biology approaches, especially but not limited to the study of the lung as a complex system. ⋯ We summarize the significant advances made in recent years using systems approaches for disease phenotyping, applied to data ranging from the molecular to clinical level, obtained from large-scale asthma and COPD networks. We describe new studies using temporal complexity patterns to characterize asthma and COPD and predict exacerbations as well as predict adverse outcomes in critical care. We highlight new methods that are emerging with this approach and discuss remaining questions that merit greater attention in the field.
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Am. J. Respir. Crit. Care Med. · Nov 2016
Calcineurin Orchestrates Lateral Transfer of Aspergillus fumigatus During Macrophage Cell Death.
Pulmonary aspergillosis is a lethal mold infection in the immunocompromised host. Understanding initial control of infection and how this is altered in the immunocompromised host are key goals for comprehension of the pathogenesis of pulmonary aspergillosis. ⋯ These observations identify programmed, necrosis-dependent lateral transfer of A. fumigatus between macrophages as an important host strategy for controlling fungal germination. This process is critically dependent on calcineurin. Our studies provide fundamental insights into the pathogenesis of pulmonary aspergillosis in the immunocompromised host.