2011 Sep 1 - Randomized, Placebo-controlled Clinical Trial of an Aerosolized β2-Agonist for Treatment of Acute Lung Injury

The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. American Journal of Respiratory and Critical Care Medicine Vol 184. pp. 561-568, (2011)
Rationale: β2-Adrenergic receptor agonists accelerate resolution of pulmonary edema in experimental and clinical studies.

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2011 Sep 1 -Fas Determines Differential Fates of Resident and Recruited Macrophages during Resolution of Acute Lung Injury

William J Janssen1, Lea Barthel1, Alaina Muldrow1, Rebecca E Oberley-Deegan1, Mark T Kearns2, Claudia Jakubzick3 and Peter M Henson4 American Journal of Respiratory and Critical Care Medicine Vol 184. pp. 547-560, (2011)
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.

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2011 Sep1 - Inhibiting Lung Elastase Activity Enables Lung Growth in Mechanically Ventilated Newborn Mice

Anne Hilgendorff1,4, Kakoli Parai1, Robert Ertsey1, Noopur Jain1, Edwin F. Navarro1, Joanna L. Peterson1, Rasa Tamosiuniene2, Mark R. Nicolls2, Barry C. Starcher3, Marlene Rabinovitch1 and Richard D. Bland1  American Journal of Respiratory and Critical Care Medicine Vol 184. pp. 537-546, (2011)
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.

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2011 Aug 15 - Shedding of Low-Density Lipoprotein Receptor–related Protein-1 in Acute Respiratory Distress Syndrome

Malgorzata Wygrecka1, Jochen Wilhelm2, Ewa Jablonska1, Dariusz Zakrzewicz1, Klaus T Preissner1, Werner Seeger2, Andreas Guenther2 and Philipp Markart2. American Journal of Respiratory and Critical Care Medicine Vol 184. pp. 438-448, (2011)
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.

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2011 Aug 15 - Characteristics and Outcomes of Ventilated Patients According to Time to Liberation from Mechanical Ventilation

Oscar Peñuelas1,2, Fernando Frutos-Vivar1,2, Cristina Fernández3, Antonio Anzueto4, Scott K. Epstein6, Carlos Apezteguía7, Marco González8, Nicolas Nin1,2, Konstantinos Raymondos9, Vinko Tomicic10, Pablo Desmery11, Yaseen Arabi12, Paolo Pelosi13, Michael Kuiper14, Manuel Jibaja15, Dimitros Matamis16, Niall D. Ferguson5, Andrés Esteban1,2 and for the Ventila Group*. American Journal of Respiratory and Critical Care Medicine Vol 184. pp. 430-437, (2011)
Rationale: A new classification of patients based on the duration of liberation of mechanical ventilation has been proposed.

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2011 Aug 15 - Airway Epithelial Transcription Factor NK2 Homeobox 1 Inhibits Mucous Cell Metaplasia and Th2 Inflammation

Yutaka Maeda1, Gang Chen1, Yan Xu1, Hans Michael Haitchi1,2, Lingling Du1, Angela R. Keiser1, Peter H. Howarth2, Donna E. Davies2, Stephen T. Holgate2 and Jeffrey A. Whitsett1.  American Journal of Respiratory and Critical Care Medicine Vol 184. pp. 421-429, (2011)
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.

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2011 Aug 1 - Routine Use of the Confusion Assessment Method for the Intensive Care Unit: A Multicenter Study

Maarten M. van Eijk1, Mark van den Boogaard2, Rob J. van Marum3, Paul Benner4, Piet Eikelenboom5,6, Marina L. Honing7, Ben van der Hoven8, Janneke Horn9, Gerbrand J. Izaks10, Annette Kalf11, Attila Karakus12, Ine A. Klijn13, Michael A. Kuiper14, Frank-Erik de Leeuw15, Tjarda de Man16, Roos C. van der Mast17, Robert-Jan Osse18, Sophia E. de Rooij19, Peter E. Spronk20, Peter H. van der Voort21, Willem A. van Gool5 and Arjen J. Slooter1. American Journal of Respiratory and Critical Care Medicine Vol 184. pp. 340-344, (2011)
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.

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2011 Aug 1 - Galectin-9 Attenuates Acute Lung Injury by Expanding CD14– Plasmacytoid Dendritic Cell–like Macrophages

Keisuke Kojima1,*, Tomohiro Arikawa2,*, Naoki Saita1,*, Eisuke Goto1, Shinsuke Tsumura1, Reina Tanaka1, Aiko Masunaga1, Toshiro Niki2,3, Souichi Oomizu2, Mitsuomi Hirashima2,3,# and Hirotsugu Kohrogi1.  American Journal of Respiratory and Critical Care Medicine Vol 184. pp. 328-339, (2011)
Rationale: Galectin (Gal)-9 plays a crucial role in the modulation of innate and adaptive immunity.

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2011 Jul 15 - Activation of CXCR2 by Extracellular Matrix Degradation Product Acetylated Pro-Gly-Pro Has Therapeutic Effects against Sepsis

Sang Doo Kim1,2, Ha Young Lee1,*, Jae Woong Shim2, Hak Jung Kim1,2, Young Hyun Yoo2, Joon Seong Park3, Suk-Hwan Baek4, Brian A. Zabel5 and Yoe-Sik Bae1,2. American Journal of Respiratory and Critical Care Medicine Vol 184. pp. 243-251, (2011). Published ahead of print on April 21, 2011, doi:10.1164/rccm.201101-0004OC
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.

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2011 Jul 1 - Peroxisome Proliferator–activated Receptor –induced T Cell Apoptosis Reduces Survival during Polymicrobial Sepsis

Martina Victoria Schmidt1, Patrick Paulus2, Anne-Marie Kuhn1, Andreas Weigert1, Virginie Morbitzer1, Kai Zacharowski2, Volkhard A. J. Kempf3, Bernhard Brüne1 and Andreas von Knethen1. Published ahead of print on February 25, 2011, doi:10.1164/rccm.201010-1585OC. American Journal of Respiratory and Critical Care Medicine Vol 184. pp. 64-74, (2011)
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.

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2011 Jun 15 - Comparison of Medical Admissions to Intensive Care Units in the United States and United Kingdom

Hannah Wunsch1,2, Derek C. Angus3, David A. Harrison4, Walter T. Linde-Zwirble5 and Kathryn M. Rowan4. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 1666-1673, (2011)
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.

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2011 Jun 15 - Active and Passive Cigarette Smoking and Acute Lung Injury after Severe Blunt Trauma

Carolyn S. Calfee1–4, Michael A. Matthay1–3, Mark D. Eisner1–4, Neal Benowitz4,5, Mariah Call6, Jean-François Pittet7 and Mitchell J. Cohen6. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 1660-1665, (2011)
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.

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2011 Feb - Recombinant Tissue Factor Pathway Inhibitor in Severe Community-acquired Pneumonia: A Randomized Trial

Richard G. Wunderink1, Pierre-François Laterre2, Bruno Francois3, Dominique Perrotin4, Antonio Artigas5, Luis Otero Vidal6, Suzana M. Lobo7, Jorge San Juan8, Sung Chul Hwang9, Thierry Dugernier10, Steven LaRosa11, Xavier Wittebole2, Jean-Francois Dhainaut12, Christopher Doig13, Meryl H. Mendelson14, Christian Zwingelstein15, Guoqin Su14, Steven Opal11 on behalf of the CAPTIVATE Trial Group*. Am. J. Respir. Crit. Care Med., June 1, 2011; 183(11): 1449 - 1450. 
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.

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2011 Jun 1 - Haplotype Association Mapping of Acute Lung Injury in Mice Implicates Activin A Receptor, Type 1

George D. Leikauf1, Vincent J. Concel1, Pengyuan Liu2, Kiflai Bein1, Annerose Berndt3, Koustav Ganguly1, An Soo Jang1,4, Kelly A. Brant1, Maggie Dietsch5, Hannah Pope-Varsalona1, Richard A. Dopico, Jr.1, Y. P. Peter Di1, Qian Li5, Louis J. Vuga6, Mario Medvedovic5, Naftali Kaminski6, Ming You2 and Daniel R. Prows7,8. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 1499-1509, (2011)
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.

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2011 Jun 1 - Leptin Promotes Fibroproliferative Acute Respiratory Distress Syndrome by Inhibiting Peroxisome Proliferator–activated Receptor-Gamma

Manu Jain1,2,*, G. R. Scott Budinger1,2,*, Amy Lo3, Daniela Urich1,2, Stephanie E. Rivera1,2, Asish K. Ghosh1,4, Angel Gonzalez1,2, Sergio E. Chiarella1,2, Katie Marks1, Helen K. Donnelly1,2, Saul Soberanes1,2, John Varga1,5, Kathryn A. Radigan1,2, Navdeep S. Chandel1,2 and Gökhan M. Mutlu1,2. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 1490-1498, (2011)
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.

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2011 May 1 - Corticosteroid Treatment in Critically Ill Patients with Pandemic Influenza A/H1N1 2009 Infection: Analytic Strategy Using Propensity Scores

Sung-Han Kim1, Sang-Bum Hong2, Sung-Choel Yun3, Won-Il Choi4, Jong-Joon Ahn5, Young Joo Lee6, Heung-Bum Lee7, Chae-Man Lim2, Younsuck Koh2 for the Korean Society of Critical Care Medicine H1N1 Collaborative* Published ahead of print on March 4, 2011, doi:10.1164/rccm.201101-0110OC. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 1207-1214, (2011)
Rationale: Administration of adjuvant corticosteroids to patients with pandemic influenza A/H1N1 2009 (pH1N1) may reduce inflammation and improve outcomes.

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2011 May 1 - Early Corticosteroids in Severe Influenza A/H1N1 Pneumonia and Acute Respiratory Distress Syndrome

Christian Brun-Buisson1,2,3, Jean-Christophe M. Richard4, Alain Mercat5, Anne C. M. Thiébaut3,6, Laurent Brochard1,2,7 for the REVA-SRLF A/H1N1v 2009 Registry Group* Published ahead of print on March 4, 2011, doi:10.1164/rccm.201101-0135OC. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 1200-1206, (2011)
Rationale: Despite their controversial role, corticosteroids are often administered to patients with adult respiratory distress syndrome (ARDS) secondary to viral pneumonia.

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2011 May 1 - Lung Regional Metabolic Activity and Gas Volume Changes Induced by Tidal Ventilation in Patients with Acute Lung Injury

Giacomo Bellani1,2, Luca Guerra3,4, Guido Musch5, Alberto Zanella1,2, Nicolò Patroniti1,2, Tommaso Mauri1,2, Cristina Messa3,4,6 and Antonio Pesenti1,2. Published ahead of print on January 21, 2011, doi:10.1164/rccm.201008-1318OC. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 1193-1199, (2011)
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.

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2011 Apr 15 - Recombinant Surfactant Protein C–based Surfactant for Patients with Severe Direct Lung Injury

Roger G. Spragg1,*, Friedemann J. H. Taut2,*, James F. Lewis3, Peter Schenk4, Clemens Ruppert5, Nathan Dean6, Kenneth Krell7, Andreas Karabinis8 and Andreas Günther5. Published ahead of print on December 10, 2010, doi:10.1164/rccm.201009-1424OC. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 1055-1061, (2011)
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.

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2011 Apr 15 - Epithelial Cell Death Is an Important Contributor to Oxidant-mediated Acute Lung Injury

G. R. Scott Budinger1,2,*, Gökhan M. Mutlu1,*, Daniela Urich2, Saul Soberanes1, Leonard J. Buccellato1, Keenan Hawkins1, Sergio E. Chiarella1, Kathryn A. Radigan1, James Eisenbart1, Hemant Agrawal1, Sara Berkelhamer3, Siegfried Hekimi4, Jianke Zhang5, Harris Perlman1, Paul T. Schumacker1,2,3, Manu Jain1 and Navdeep S. Chandel1,2. Published ahead of print on October 19, 2010, doi:10.1164/rccm.201002-0181OC. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 1043-1054, (2011)
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.

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