American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Nov 2018
Drug-Penetration Gradients Associated with Acquired Drug Resistance in Patients with Tuberculosis.
Acquired resistance is an important driver of multidrug-resistant tuberculosis (TB), even with good treatment adherence. However, exactly what initiates the resistance and how it arises remain poorly understood. ⋯ These data inform interventional strategies relevant to drug delivery, dosing, and diagnostics to prevent the development of acquired resistance. The role of high intracavitary penetration as a biomarker of antibiotic efficacy, when assessing new regimens, requires clarification.
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Am. J. Respir. Crit. Care Med. · Nov 2018
Lung Dendritic Cells Drive Natural Killer Cytotoxicity in Chronic Obstructive Pulmonary Disease via IL-15Rα.
Lung natural killer cells (NKs) kill a greater percentage of autologous lung parenchymal cells in chronic obstructive pulmonary disease (COPD) than in nonobstructed smokers. To become cytotoxic, NKs require priming, typically by dendritic cells (DCs), but whether priming occurs in the lungs in COPD is unknown. ⋯ Heightened NK cytotoxicity against lung epithelial cells in COPD results primarily from lung DC-mediated priming via IL-15 trans-presentation on IL-15Rα. Future studies are required to test whether increased NK cytotoxicity contributes to COPD pathogenesis.
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Am. J. Respir. Crit. Care Med. · Nov 2018
Abrupt Deflation after Sustained Inflation Causes Lung Injury.
Ventilator management in acute respiratory distress syndrome usually focuses on setting parameters, but events occurring at ventilator disconnection are not well understood. ⋯ Abrupt deflation after sustained inflation can cause acute lung injury. It seems to be mediated by acute left ventricular decompensation (caused by increased left ventricular preload and afterload) that elevates pulmonary microvascular pressure; this directly injures the endothelium and causes edema, which is potentiated by the surge in pulmonary perfusion.