American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Dec 2015
TOLLIP, MUC5B and the Response to N-acetylcysteine Among Individuals with Idiopathic Pulmonary Fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown etiology. The genes TOLLIP and MUC5B play important roles in lung host defense, which is an immune process influenced by oxidative signaling. Whether polymorphisms in TOLLIP and MUC5B modify the effect of immunosuppressive and antioxidant therapy in individuals with IPF is unknown. ⋯ NAC may be an efficacious therapy for individuals with IPF with an rs3750920 (TOLLIP) TT genotype, but it was associated with a trend toward harm in those with a CC genotype. A genotype-stratified prospective clinical trial should be conducted before any recommendation regarding the use of off-label NAC to treat IPF.
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Am. J. Respir. Crit. Care Med. · Dec 2015
X-Box Binding Protein 1 Modulates Innate Immune Responses of Cystic Fibrosis Alveolar Macrophages.
Alveolar macrophages (AMs) play a key role in host defense to inhaled bacterial pathogens, in part by secreting inflammatory mediators. Cystic fibrosis (CF) airways exhibit a persistent, robust inflammatory response that may contribute to the pathophysiology of CF. Recent findings have linked endoplasmic reticulum stress responses mediated by inositol-requiring enzyme 1α-dependent messenger RNA splicing (activation) of X-box-binding protein-1 (XBP-1s) to inflammation in peripheral macrophages. However, the role of XBP-1s in CF AM function is not known. ⋯ These findings suggest that AMs contribute to the robust inflammation of CF airways via an up-regulation of XBP-1s-mediated cytokine production.
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Am. J. Respir. Crit. Care Med. · Dec 2015
ReviewPotential Strategies to Prevent Ventilator-Associated Events.
The Centers for Disease Control and Prevention (CDC) released ventilator-associated event (VAE) definitions in 2013. The new definitions were designed to track episodes of sustained respiratory deterioration in mechanically ventilated patients after a period of stability or improvement. More than 2,000 U. ⋯ Potential strategies include avoiding intubation, minimizing sedation, paired daily spontaneous awakening and breathing trials, early exercise and mobility, low tidal volume ventilation, conservative fluid management, and conservative blood transfusion thresholds. Interventional studies have thus far affirmed that minimized sedation, paired daily spontaneous awakening and breathing trials, and conservative fluid management can reduce VAE rates and improve patient-centered outcomes. Further studies are needed to evaluate the impact of the other proposed interventions, to identify additional modifiable risk factors for VAEs, and to measure whether combining strategies into VAE prevention bundles confers additional benefits over implementing one or more of these interventions in isolation.