American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Dec 2019
Pulmonary Aptamer Signatures in Children's Interstitial and Diffuse Lung Disease.
Rationale: Biomarker signatures are needed in children with children's interstitial and diffuse lung disease (chILD) to improve diagnostic approaches, increase our understanding of disease pathogenesis, monitor disease progression, and develop new treatment strategies. Proteomic technology using SOMAmer (Slow Off-rate Modified Aptamer) nucleic acid-based protein-binding reagents allows for biomarker discovery. Objectives: We hypothesized that proteins and protein pathways in BAL fluid (BALF) would distinguish children with neuroendocrine cell hyperplasia of infancy (NEHI), surfactant dysfunction mutations, and other chILD diagnoses and control subjects. ⋯ Proteins associated with pulmonary fibrosis and inflammation were associated with the surfactant dysfunction group but not the NEHI group. Using hierarchical clustering analysis, two distinct NEHI endotypes were identified. Conclusions: Distinct proteins and protein pathways can be determined from BALF of children with chILD, and these hold promise to further our understanding of chILD.
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Am. J. Respir. Crit. Care Med. · Dec 2019
Inflammation without Vascular Leakage. Science Fiction No Longer?
Vascular leakage is a characteristic of critical illnesses such as septic shock and acute respiratory distress syndrome. It results in hypotension and tissue edema and contributes to organ dysfunction. It has long been taught that increased vascular permeability is a natural consequence of inflammation; in particular, many clinicians believe that it occurs inevitably during leukocyte recruitment to a site of infection. ⋯ The molecular mechanisms underpinning these processes-allowing leukocytes to exit the circulation without increasing vascular permeability-are starting to be elucidated and establish vascular leakage as a viable therapeutic target. Several preclinical studies indicate that vascular leakage can be reduced without impairing cytokine production, leukocyte recruitment, and pathogen clearance. The realization that leukocyte traffic and vascular permeability can be regulated separately should spur development of therapies that decrease vascular leakage and tissue edema without compromising the immune response.