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
ReviewPro: Physiologic Responsiveness Should Guide Entry into Randomized Controlled Trials.
Most randomized trials in critical care report no mortality benefit; this may reflect competing pathogenic mechanisms, patient heterogeneity, or true ineffectiveness of interventions. We hypothesize that in acute respiratory distress syndrome (ARDS), randomizing only those patients who show a favorable physiological response to an intervention would help ensure that only those likely to benefit would be entered into the study. ⋯ It would also lessen the chances of exposing patients to treatments that are unlikely to help or that could cause harm. We present a reanalysis of randomized clinical trials of positive end-expiratory pressure in ARDS that support this hypothesis.