American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Feb 2014
Glutaredoxin-1 Attenuates S-glutathionylation of the Death Receptor Fas and Decreases Resolution of Pseudomonas aeruginosa Pneumonia.
The death receptor Fas is critical for bacterial clearance and survival of mice after Pseudomonas aeruginosa infection. ⋯ These results suggest that S-glutathionylation of Fas within the lung epithelium enhances epithelial apoptosis and promotes clearance of P. aeruginosa and that glutaredoxin-1 impairs bacterial clearance and increases the severity of pneumonia in association with deglutathionylation of Fas.
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Am. J. Respir. Crit. Care Med. · Feb 2014
Estimates of the Need for Palliative Care Consultation across United States ICUs Using a Trigger-based Model.
Use of triggers for palliative care consultation has been advocated in intensive care units (ICUs) to ensure appropriate specialist involvement for patients at high risk of unmet palliative care needs. The volume of patients meeting these triggers, and thus the potential workload for providers, is unknown. ⋯ Approximately one in seven ICU admissions met triggers for palliative care consultation using a single set of triggers, with an upper estimate of one in five patients using multiple sets of triggers; these estimates were consistent across different types of ICUs and individual units. These results may inform staffing requirements for providers to ensure delivery of specialized palliative care to ICU patients nationally.
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Am. J. Respir. Crit. Care Med. · Feb 2014
ReviewNovel and Emerging Therapies for Pulmonary Hypertension.
The development of therapeutic concepts in pulmonary hypertension (PH) is intimately linked with the unraveling of pathogenetic sequelae. This perspective highlights advances in our understanding of the regulation of vasomotion and vascular remodeling that have led to "reverse-remodeling" and regenerative strategies as novel treatment concepts. Progress has been made in understanding redox-dependent signaling; inflammatory sequelae; and transcription factor, ion channel, and metabolic abnormalities, as well as growth factor-dependent hyperproliferation that underlies PH. ⋯ The proangiogenic potential of genetically engineered mesenchymal stem cells and endothelial progenitor cells has been explored as a regenerative strategy. The progress that has been made in identifying important cellular and molecular mechanisms and applying this knowledge to novel therapies is largely restricted to group 1 PH. However, understanding the molecular sequelae underlying PH in groups 2 through 5 PH is also urgently needed.
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Am. J. Respir. Crit. Care Med. · Feb 2014
Mucosal Immune Responses Predict Clinical Outcomes during Influenza Infection Independently of Age and Viral Load.
Children are an at-risk population for developing complications following influenza infection, but immunologic correlates of disease severity are not understood. We hypothesized that innate cellular immune responses at the site of infection would correlate with disease outcome. ⋯ An innate profile was identified that correlated with disease progression independent of viral dynamics and age. The airways and blood displayed dramatically different immune profiles emphasizing the importance of cellular migration and localized immune phenotypes.