2011 Sep 1 - Randomized, Placebo-controlled Clinical Trial of an Aerosolized β2-Agonist for Treatment of Acute Lung Injury
Rationale: β2-Adrenergic receptor agonists accelerate resolution of pulmonary edema in experimental and clinical studies.
2011 Sep 1 -Fas Determines Differential Fates of Resident and Recruited Macrophages during Resolution of Acute Lung Injury
Rationale: During acute lung injury (ALI) the macrophage pool expands markedly as inflammatory monocytes migrate from the circulation to the airspaces. As inflammation resolves, macrophage numbers return to preinjury levels and normal tissue structure and function are restored.
2011 Sep1 - Inhibiting Lung Elastase Activity Enables Lung Growth in Mechanically Ventilated Newborn Mice
Rationale: Mechanical ventilation with O2-rich gas (MV-O2) offers life-saving treatment for respiratory failure, but also promotes lung injury. We previously reported that MV-O2 of newborn mice increased lung elastase activity, causing elastin degradation and redistribution of elastic fibers from septal tips to alveolar walls. These changes were associated with transforming growth factor (TGF)-β activation and increased apoptosis leading to defective alveolarization and lung growth arrest, as seen in neonatal chronic lung disease.
2011 Aug 15 - Shedding of Low-Density Lipoprotein Receptor–related Protein-1 in Acute Respiratory Distress Syndrome
Rationale: Low-density lipoprotein receptor–related protein-1 (LRP-1) mediates the endocytic clearance of various proteinases, including matrix metalloproteinases (MMPs). The ectodomain of LRP-1 can be shed from the cell surface, releasing a soluble form of this receptor (sLRP-1), which antagonizes ligand endocytosis by cellular LRP-1.
2011 Aug 15 - Characteristics and Outcomes of Ventilated Patients According to Time to Liberation from Mechanical Ventilation
Rationale: A new classification of patients based on the duration of liberation of mechanical ventilation has been proposed.
2011 Aug 15 - Airway Epithelial Transcription Factor NK2 Homeobox 1 Inhibits Mucous Cell Metaplasia and Th2 Inflammation
Rationale: Airway mucous cell metaplasia and chronic inflammation are pathophysiological features that influence morbidity and mortality associated with asthma and other chronic pulmonary disorders. Elucidation of the molecular mechanisms regulating mucous metaplasia and hypersecretion provides the scientific basis for diagnostic and therapeutic opportunities to improve the care of chronic pulmonary diseases.
2011 Aug 1 - Routine Use of the Confusion Assessment Method for the Intensive Care Unit: A Multicenter Study
Rationale: Delirium is often unrecognized in ICU patients and associated with poor outcome. Screening for ICU delirium is recommended by several medical organizations to improve early diagnosis and treatment. The Confusion Assessment Method for the ICU (CAM-ICU) has high sensitivity and specificity for delirium when administered by research nurses. However, test characteristics of the CAM-ICU as performed in routine practice are unclear.
2011 Aug 1 - Galectin-9 Attenuates Acute Lung Injury by Expanding CD14– Plasmacytoid Dendritic Cell–like Macrophages
Rationale: Galectin (Gal)-9 plays a crucial role in the modulation of innate and adaptive immunity.
2011 Jul 15 - Activation of CXCR2 by Extracellular Matrix Degradation Product Acetylated Pro-Gly-Pro Has Therapeutic Effects against Sepsis
Rationale: Acetylated Pro-Gly-Pro (Ac-PGP) is an endogenous degradation product of extracellular collagen that binds to leukocyte-expressed chemoattractant receptor CXCR2. Although certain agents that block CXCR2-mediated signaling protect against experimental sepsis, the roles of Ac-PGP and CXCR2 in sepsis are unclear.
2011 Jul 1 - Peroxisome Proliferator–activated Receptor –induced T Cell Apoptosis Reduces Survival during Polymicrobial Sepsis
Rationale: Despite intensive research, sepsis displays the most prevalent cause of death on intensive care units. The hallmark of sepsis is an overshooting T-cell death that reduces host defense mechanisms and that is associated with poor patient survival. Previous in vitro studies revealed that the expression of the transcription factor peroxisome proliferator–activated receptor (PPAR) was increased in isolated T cells of patients with sepsis.
2011 Jun 15 - Comparison of Medical Admissions to Intensive Care Units in the United States and United Kingdom
Rationale: The United States has seven times as many intensive care unit (ICU) beds per capita as the United Kingdom; the effect on care of critically ill patients is unknown.
Rationale: Cigarette smoking has been demonstrated in laboratory studies to have effects on lung epithelial and endothelial function similar to those observed in acute lung injury (ALI). However, the association between active and passive cigarette smoke exposure and susceptibility to ALI has not been prospectively studied.
2011 Feb - Recombinant Tissue Factor Pathway Inhibitor in Severe Community-acquired Pneumonia: A Randomized Trial
Rationale: Severe community-acquired pneumonia (sCAP) is a leading cause of death worldwide. Adjunctive therapies for sCAP are needed to further improve outcome. A systemic inhibitor of coagulation, tifacogin (recombinant human tissue factor pathway inhibitor) seemed to provide mortality benefit in the sCAP subgroup of a previous sepsis trial.
2011 Jun 1 - Haplotype Association Mapping of Acute Lung Injury in Mice Implicates Activin A Receptor, Type 1
Rationale: Because acute lung injury is a sporadic disease produced by heterogeneous precipitating factors, previous genetic analyses are mainly limited to candidate gene case-control studies.
2011 Jun 1 - Leptin Promotes Fibroproliferative Acute Respiratory Distress Syndrome by Inhibiting Peroxisome Proliferator–activated Receptor-Gamma
Rationale: Diabetic patients have a lower incidence of acute respiratory distress syndrome (ARDS), and those who develop ARDS are less likely to die. The mechanisms that underlie this protection are unknown.
2011 May 1 - Corticosteroid Treatment in Critically Ill Patients with Pandemic Influenza A/H1N1 2009 Infection: Analytic Strategy Using Propensity Scores
Rationale: Administration of adjuvant corticosteroids to patients with pandemic influenza A/H1N1 2009 (pH1N1) may reduce inflammation and improve outcomes.
2011 May 1 - Early Corticosteroids in Severe Influenza A/H1N1 Pneumonia and Acute Respiratory Distress Syndrome
Rationale: Despite their controversial role, corticosteroids are often administered to patients with adult respiratory distress syndrome (ARDS) secondary to viral pneumonia.
2011 May 1 - Lung Regional Metabolic Activity and Gas Volume Changes Induced by Tidal Ventilation in Patients with Acute Lung Injury
Rationale: During acute lung injury (ALI), mechanical ventilation can aggravate inflammation by promoting alveolar distension and cyclic recruitment–derecruitment. As an estimate of the intensity of inflammation, metabolic activity can be measured by positron emission tomography imaging of [18F]fluoro-2-deoxy-D-glucose.
2011 Apr 15 - Recombinant Surfactant Protein C–based Surfactant for Patients with Severe Direct Lung Injury
Rationale: Patients with acute lung injury have impaired function of the lung surfactant system. Prior clinical trials have shown that treatment with exogenous recombinant surfactant protein C (rSP-C)-based surfactant results in improvement in blood oxygenation and have suggested that treatment of patients with severe direct lung injury may decrease mortality.
2011 Apr 15 - Epithelial Cell Death Is an Important Contributor to Oxidant-mediated Acute Lung Injury
Rationale: Acute lung injury and the acute respiratory distress syndrome are characterized by increased lung oxidant stress and apoptotic cell death. The contribution of epithelial cell apoptosis to the development of lung injury is unknown.