American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Oct 2016
Integrated Genomics Reveals Convergent Transcriptomic Networks Underlying COPD and IPF.
Despite shared environmental exposures, idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease are usually studied in isolation, and the presence of shared molecular mechanisms is unknown. ⋯ Our results suggest convergent transcriptional regulatory hubs in diseases as varied phenotypically as chronic obstructive pulmonary disease and IPF and suggest that these hubs may represent shared key responses of the lung to environmental stresses.
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Am. J. Respir. Crit. Care Med. · Oct 2016
ARDS Neutrophils Have a Distinct Phenotype and are Resistant to Phosphoinositide 3-kinase Inhibition.
Acute respiratory distress syndrome is refractory to pharmacological intervention. Inappropriate activation of alveolar neutrophils is believed to underpin this disease's complex pathophysiology, yet these cells have been little studied. ⋯ Acute respiratory distress syndrome blood and alveolar neutrophils display a distinct primed prosurvival profile and transcriptional signature. The enhanced respiratory burst was phosphoinositide 3-kinase-dependent but delayed apoptosis and the altered transcriptional profile were not. These unexpected findings cast doubt over the utility of phosphoinositide 3-kinase inhibition in acute respiratory distress syndrome and highlight the importance of evaluating novel therapeutic strategies in patient-derived cells.
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Am. J. Respir. Crit. Care Med. · Oct 2016
Multicenter StudyAbnormal Glucose Tolerance in Infants and Young Children with Cystic Fibrosis.
In cystic fibrosis, abnormal glucose tolerance is associated with decreased lung function and worsened outcomes. Translational evidence indicates that abnormal glucose tolerance may begin in early life. ⋯ Abnormal glucose tolerance is notably prevalent among young children with cystic fibrosis. Children with cystic fibrosis lack the normal increase in insulin secretion that occurs in early childhood despite increased glucose. These findings demonstrate that glycemic abnormalities begin very early in cystic fibrosis, possibly because of insufficient insulin secretion.