Lorraine B Ware

Vanderbilt University, Нашвилл, Michigan, United States

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Publications (271)1464.07 Total impact

  • David R Janz, Lorraine B Ware
    12/2015; 3(1). DOI:10.1186/s40560-015-0086-3
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    ABSTRACT: Tissue factor (TF) initiates the extrinsic coagulation cascade in response to tissue injury leading to local fibrin deposition. Low levels of TF in mice are associated with increased severity of acute lung injury (ALI) following intra-tracheal (IT) lipopolysaccharide (LPS) administration. However, the cellular sources of the TF required for protection from LPS-induced ALI remain unknown. In the current study, transgenic mice with cell-specific deletions of TF in the lung epithelium or myeloid cells were treated with IT LPS to determine the cellular sources of TF important in direct ALI. Cell-specific deletion of TF in the lung epithelium reduced total lung TF expression to 39% of wild-type levels at baseline and to 29% of wild-type levels after IT LPS. In contrast, there was no reduction of TF with myeloid cell TF deletion. Mice lacking myeloid cell TF (TF(Δmye)) did not differ from wild-type mice in coagulation, inflammation, permeability, or hemorrhage. However, mice lacking lung epithelial TF (TF(ΔLEpi)) had increased tissue injury, impaired activation of coagulation in the airspace, disrupted alveolar permeability, and increased alveolar hemorrhage after IT LPS. Deletion of epithelial TF did not affect alveolar permeability in an indirect model of ALI caused by systemic LPS infusion. These studies demonstrate that the lung epithelium is the primary source of TF in the lung contributing 60-70% of total lung TF and that lung epithelial but not myeloid TF may be protective in direct ALI.
    American Journal of Respiratory Cell and Molecular Biology 04/2015; DOI:10.1165/rcmb.2014-0179OC · 4.11 Impact Factor
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    ABSTRACT: Primary graft dysfunction (PGD) is a major cause of early mortality after lung transplant. We aimed to define objective estimates of PGD risk based on readily available clinical variables, using a prospective study of 11 centers in the Lung Transplant Outcomes Group (LTOG). Derivation included 1255 subjects from 2002 to 2010; with separate validation in 382 subjects accrued from 2011 to 2012. We used logistic regression to identify predictors of grade 3 PGD at 48/72 h, and decision curve methods to assess impact on clinical decisions. 211/1255 subjects in the derivation and 56/382 subjects in the validation developed PGD. We developed three prediction models, where low-risk recipients had a normal BMI (18.5-25 kg/m(2) ), chronic obstructive pulmonary disease/cystic fibrosis, and absent or mild pulmonary hypertension (mPAP<40 mmHg). All others were considered higher-risk. Low-risk recipients had a predicted PGD risk of 4-7%, and high-risk a predicted PGD risk of 15-18%. Adding a donor-smoking lung to a higher-risk recipient significantly increased PGD risk, although risk did not change in low-risk recipients. Validation demonstrated that probability estimates were generally accurate and that models worked best at baseline PGD incidences between 5% and 25%. We conclude that valid estimates of PGD risk can be produced using readily available clinical variables. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
    American Journal of Transplantation 04/2015; DOI:10.1111/ajt.13262 · 6.19 Impact Factor
  • 03/2015; 12 Suppl 1:S77. DOI:10.1513/AnnalsATS.201411-530MG
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    ABSTRACT: Thombomodulin (TM) is an activator of protein C and a biomarker for endothelial injury. We hypothesized that (1) elevated plasma levels would be associated with clinical outcomes and (2) polymorphisms in the TM gene would be associated with plasma levels. We studied 449 patients enrolled in the Fluid and Catheter Treatment Trial (FACTT) for whom both plasma and DNA were available. We used logistic regression and receiver operator curves (ROC) to test for associations between soluble TM (sTM) and mortality at 60 days. Plasma sTM levels were higher in non-survivors than survivors at baseline [median 147 (IQR, 95-218) vs. 89 (56-129) ng/mL, p < 0.0001] and on day 3 after study enrollment [205 (146-302) vs. 127 (85-189), p < 0.0001]. The odds of death increased by 2.4 (95 % CI 1.5-3.8, p < 0.001), and by 2.8 (1.7-4.7, P < 0.001) for every log increase in baseline and day 3 sTM levels, respectively, after adjustment for age, race, gender, severity of illness, fluid management strategy, baseline creatinine, and non-pulmonary sepsis as the primary cause of ARDS. By ROC analysis, plasma sTM levels discriminated between non-survivors and survivors [AUC = 72 % (66-78 %) vs. AUC = 54 % for severity based on Berlin criteria). Addition of sTM improved discrimination based on APACHE III from 77 to 80 % (P < 0.03). sTM levels at baseline were not statistically different among subjects stratified by genotypes of tag SNPs in the TM gene. Higher plasma sTM levels are associated with increased mortality in ARDS. The lack of association between the sTM levels and genetic variants suggests that the increased levels of sTM may reflect severity of endothelial damage rather than genetic heterogeneity. These findings underscore the importance of endothelial injury in ARDS pathogenesis and suggest that, in combination with clinical markers, sTM could contribute to risk stratification.
    Intensive Care Medicine 02/2015; 41(3). DOI:10.1007/s00134-015-3648-x · 5.54 Impact Factor
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    Julie A. Bastarache, James L. Wynn, Lorraine B. Ware
    02/2015; 16(3). DOI:10.1016/j.ebiom.2015.01.019
  • Journal of Allergy and Clinical Immunology 02/2015; 135(2):AB162. DOI:10.1016/j.jaci.2014.12.1469 · 11.25 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2015; 135(2):AB164. DOI:10.1016/j.jaci.2014.12.1473 · 11.25 Impact Factor
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    ABSTRACT: Platelet activation plays an active role in the pathogenesis of acute respiratory distress syndrome. In our prior study of 575 patients at high risk for acute respiratory distress syndrome, concurrent statin and aspirin use was associated with reduced acute respiratory distress syndrome. However, the largest study (n = 3,855) to date found no significant benefit of prehospital aspirin in a lower-risk population when adjusted for the propensity for aspirin use. We aimed to determine whether prehospital aspirin use is associated with decreased acute respiratory distress syndrome in patients at high risk for acute respiratory distress syndrome after adjusting for the propensity to receive aspirin. Secondary analysis of patients enrolled prospectively in the Validating Acute Lung Injury Markers for Diagnosis study. A total of 1,149 critically ill patients (≥ 40 years old) admitted to the medical or surgical ICUs of an academic tertiary care hospital including 575 previously reported patients as well as additional patients who were enrolled after completion of the prior statin and aspirin study. None. Of 1,149 patients, 368 (32%) developed acute respiratory distress syndrome during the first 4 ICU days and 287 (25%) patients had prehospital aspirin use. Patients with prehospital aspirin had significantly lower prevalence of acute respiratory distress syndrome (27% vs 34%; p = 0.034). In a multivariable, propensity-adjusted analysis including age, gender, race, sepsis, and Acute Physiology and Chronic Health Evaluation score II, prehospital aspirin use was associated with a decreased risk of acute respiratory distress syndrome (odds ratio, 0.66; 95% CI, 0.46-0.94) in the entire cohort and in a subgroup of 725 patients with sepsis (odds ratio, 0.60; 95% CI, 0.41-0.90). In this selected cohort of critically ill patients, prehospital aspirin use was independently associated with a decreased risk of acute respiratory distress syndrome even after adjusting for the propensity of prehospital aspirin use. These findings support the need for prospective clinical trials to determine whether aspirin may be beneficial for the prevention of clinical acute respiratory distress syndrome.
    Critical Care Medicine 12/2014; 43(4). DOI:10.1097/CCM.0000000000000789 · 6.15 Impact Factor
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    ABSTRACT: Background:The Acute Respiratory Distress Syndrome (ARDS) is a heterogeneous syndrome that encompasses lung injury from both direct and indirect sources. Direct ARDS (pneumonia, aspiration) has been hypothesized to cause more severe lung epithelial injury than indirect ARDS (e.g. non-pulmonary sepsis); however, this hypothesis has not been well-studied in humans. Methods:We measured plasma biomarkers of lung epithelial and endothelial injury and inflammation in a single center study of 100 patients with ARDS and severe sepsis, and in a secondary analysis of 853 ARDS patients drawn from a multicenter randomized controlled trial. Biomarker levels in patients with direct vs indirect ARDS were compared in both cohorts. Results:In both studies, direct ARDS patients had significantly higher levels of a biomarker of lung epithelial injury (surfactant protein-D) and significantly lower levels of a biomarker of endothelial injury (angiopoietin-2), compared with indirect ARDS patients. These associations were robust to adjustment for severity of illness and ARDS severity. In the multicenter study, direct ARDS patients also had lower levels of von Willebrand factor antigen and interleukins 6 and 8, markers of endothelial injury and inflammation, respectively. The prognostic value of the biomarkers was similar in direct and indirect ARDS. Conclusions:Direct lung injury in humans is characterized by a molecular phenotype consistent with more severe lung epithelial injury and less severe endothelial injury. The opposite pattern was identified in indirect lung injury. Clinical trials of novel therapies targeted specifically at the lung epithelium or endothelium may benefit from preferentially enrolling patients with direct or indirect ARDS, respectively. The Acute Respiratory Distress Syndrome (ARDS) is a heterogeneous syndrome that encompasses lung injury from both direct and indirect sources. Direct ARDS (pneumonia, aspiration) has been hypothesized to cause more severe lung epithelial injury than indirect ARDS (e.g. non-pulmonary sepsis); however, this hypothesis has not been well-studied in humans. We measured plasma biomarkers of lung epithelial and endothelial injury and inflammation in a single center study of 100 patients with ARDS and severe sepsis, and in a secondary analysis of 853 ARDS patients drawn from a multicenter randomized controlled trial. Biomarker levels in patients with direct vs indirect ARDS were compared in both cohorts. In both studies, direct ARDS patients had significantly higher levels of a biomarker of lung epithelial injury (surfactant protein-D) and significantly lower levels of a biomarker of endothelial injury (angiopoietin-2), compared with indirect ARDS patients. These associations were robust to adjustment for severity of illness and ARDS severity. In the multicenter study, direct ARDS patients also had lower levels of von Willebrand factor antigen and interleukins 6 and 8, markers of endothelial injury and inflammation, respectively. The prognostic value of the biomarkers was similar in direct and indirect ARDS. Direct lung injury in humans is characterized by a molecular phenotype consistent with more severe lung epithelial injury and less severe endothelial injury. The opposite pattern was identified in indirect lung injury. Clinical trials of novel therapies targeted specifically at the lung epithelium or endothelium may benefit from preferentially enrolling patients with direct or indirect ARDS, respectively.
    Chest 12/2014; DOI:10.1378/chest.14-2454 · 7.13 Impact Factor
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    ABSTRACT: Rationale: Primary graft dysfunction (PGD) causes early mortality after lung transplantation and may contribute to late graft failure. No effective treatments exist. The pathogenesis of PGD is unclear, though both neutrophils and activated platelets have been implicated. We hypothesized that neutrophil extracellular traps (NETs) contribute to lung injury in PGD in a platelet-dependent manner. Objectives: To study NETs in experimental models of PGD and in lung transplant patients. Methods: Two experimental murine PGD models were studied: hilar clamp (HC) and orthotopic lung transplantation after prolonged cold ischemia (OLT-PCI). NETs were assessed by immunofluorescence microscopy and ELISA. Platelet activation was inhibited with aspirin, and NETs were disrupted with deoxyribonuclease (DNaseI). NETs were also measured in bronchoalveolar lavage fluid (BALF) and plasma from lung transplant patients with and without PGD. Measurements and Main Results: NETs were increased after either HC or OLT-PCI compared to surgical controls. Activation and intrapulmonary accumulation of platelets were increased in OLT-PCI, and platelet inhibition reduced NETs and lung injury and improved oxygenation. Disruption of NETs by intrabronchial administration of DNaseI also reduced lung injury and improved oxygenation. In BALF from human lung transplant recipients, NETs were more abundant in patients with PGD. Conclusions: NETs accumulate in the lung in both experimental and clinical PGD. In experimental PGD, NET formation is platelet-dependent, and disruption of NETs with DNaseI reduces lung injury. These data are the first description of a pathogenic role for NETs in solid organ transplantation and suggest that NETs are a promising therapeutic target in PGD.
    American Journal of Respiratory and Critical Care Medicine 12/2014; 191(4). DOI:10.1164/rccm.201406-1086OC · 11.99 Impact Factor
  • David R. Janz, Lorraine B. Ware
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    ABSTRACT: Given the high incidence and mortality of acute respiratory distress syndrome (ARDS) in critically ill patients, every practitioner needs a bedside approach both for early identification of patients at risk for ARDS and for the appropriate evaluation of patients who meet the diagnostic criteria of ARDS. Recent advances such as the Lung Injury Prediction score, the Early Acute Lung Injury score, and validation of the SpO2/Fio2 ratio for assessing the degree of hypoxemia are all practical tools to aid the practitioner in caring for patients at risk of ARDS. Copyright © 2014 Elsevier Inc. All rights reserved.
    Clinics in Chest Medicine 12/2014; DOI:10.1016/j.ccm.2014.08.007 · 2.17 Impact Factor
  • James Walter, Lorraine B Ware, Michael A Matthay
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    ABSTRACT: Multipotent mesenchymal stem (stromal) cells (MSCs) have shown promising therapeutic effects in preclinical models of both acute respiratory distress syndrome (ARDS) and sepsis. Although initial research focused on the ability of MSCs to engraft at sites of tissue injury, increasing evidence suggests that MSCs have their therapeutic effects through mechanisms unrelated to long-term incorporation into host tissue. One of the most compelling of these pathways is the ability of MSCs to interact with injured tissue through the release of soluble bioactive factors. This Review provides an overview of the general properties of MSCs, and then outlines ways in which the paracrine effects of MSCs might reduce lung injury and enhance lung repair in ARDS and sepsis. Finally, we summarise ongoing challenges in MSC research and identify areas in which the discipline might progress in the coming years. Copyright © 2014 Elsevier Ltd. All rights reserved.
    The Lancet Respiratory Medicine 12/2014; 2(12):1016-1026. DOI:10.1016/S2213-2600(14)70217-6
  • Clinics in Chest Medicine 11/2014; DOI:10.1016/j.ccm.2014.09.001 · 2.17 Impact Factor
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    ABSTRACT: Introduction: Asymptomatic relatives of patients with Familial Interstitial Pneumonia (FIP), the inherited form of Idiopathic Interstitial Pneumonia (IIP), carry increased risk for developing interstitial lung disease. Studying these at-risk individuals provides a unique opportunity to investigate early stages of FIP pathogenesis and develop predictive models of disease onset. Methods: Seventy-five asymptomatic first-degree relatives of FIP patients (mean age 50.8 years) underwent blood sampling and high-resolution chest CT (HRCT) scan in an ongoing cohort study; 72 consented to bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsies. Twenty-seven healthy individuals were used as controls. Results: Eleven of 75 at-risk subjects (14%) had evidence of interstitial changes by HRCT while 35.2% had abnormalities on transbronchial biopsies. No differences were noted in inflammatory cells in BAL between at-risk individuals and controls. At-risk subjects had increased herpesvirus DNA in cell-free BAL and evidence of herpesvirus antigen expression in alveolar epithelial cells (AECs), which correlated with expression of endoplasmic reticulum stress markers in AECs. Peripheral blood mononuclear cell and AEC telomere length were shorter in at-risk individuals than healthy controls. The minor allele frequency of the Muc5B rs35705950 promoter polymorphism was increased in at-risk subjects. Levels of several plasma biomarkers differed between at-risk subjects and controls, and correlated with abnormal HRCT scans. Conclusions: Evidence of lung parenchymal remodeling and epithelial dysfunction were identified in asymptomatic individuals at-risk for FIP. Together, these findings offer new insights into the early pathogenesis of IIP and provide an ongoing opportunity to characterize presymptomatic abnormalities that predict progression to clinical disease.
    American Journal of Respiratory and Critical Care Medicine 11/2014; DOI:10.1164/rccm.201406-1162OC · 11.99 Impact Factor
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    American Journal of Respiratory and Critical Care Medicine 11/2014; · 11.99 Impact Factor
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    ABSTRACT: Background Hemeproteins such as free myoglobin can undergo autoxidation and catalyze lipid peroxidation, increasing oxidative stress. Creatine phosphokinase (CPK) elevation is a marker for free myoglobin after myocyte damage. Since oxidative injury is a key mechanism of injury-related organ dysfunction, we hypothesized that serum CPK levels correlate with mortality and need for and duration of inotropic support, i.e. shock, among critically injured patients. Methods We conducted a retrospective review of 17,847 patients admitted to a single Trauma Intensive Care Unit over 9 years. 2,583 patients with serum CPK levels were included in the analysis. Patient data were collected continuously into an electronic ICU repository. Univariate analysis was accomplished using Spearman correlation and the Mann Whitney U test. Propensity score adjustment models accounting for potential confounders were used to assess the independent effect of CPK level on mortality, need for inotropic support, and duration of inotropic support. Results Median CPK was significantly higher in patients who died (916 [IQR 332, 2472] vs. 711 [253,1971], p= 0.004) and in those who required inotropic medications (950 [353,2525] vs. 469 [188,1220], p< 0.001). After adjusting for propensity score and potential confounders the odds of mortality increased by 1.10 (95% CI 1.02- 1.19, p= 0.020) and the odds of inotropic medication use increased by 1.30 (95% CI 1.22-1.38, p <0.001) per natural log unit increase in CPK. There was a significant association between CPK level and duration of inotropic support (Spearman's rho .237, p< 0.001) that remained significant in a propensity score adjusted model. Conclusion In critically injured patients, elevated serum CPK level is independently associated with mortality, need for inotropic medication, and duration of inotropic support. This study is the first to evaluate the relationship of CPK level and mortality in addition to surrogate measures of shock in a population of critically injured patients. If these associations are verified prospectively, there may be a role for treatment with hemeprotein reductants, such as Paracetamol, to mitigate the effects of shock and end-organ dysfunction.
    Injury 09/2014; 45(12). DOI:10.1016/j.injury.2014.09.009 · 2.46 Impact Factor
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    ABSTRACT: Rationale:Obesity and underweight are contraindications to lung transplantation based on their associations with mortality in studies performed prior to implementation of the Lung Allocation Score (LAS)-based organ allocation system in the United States. Objectives:To determine the associations of the body mass index(BMI) and plasma leptin levels with survival after lung transplantation. Methods:We used multivariable-adjusted regression models to examine associations between (1) BMI and 1-year mortality in 9,073 adults who underwent lung transplantation in the United States between May 2005 and June 2011, and (2) plasma leptin and mortality in 599 Lung Transplant Outcomes Group study participants. We measured body fat and skeletal muscle mass using whole-body dual x-ray absorptiometry in 142 adult lung transplant candidates. Measurements and Main Results: Adjusted mortality rates were similar among normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25.0-29.9) and Class I obese (BMI 30-34.9) transplant recipients. Underweight (BMI<18.5) was associated with a 35% increased rate of death (95%CI 10-66%). Class II-III obesity (BMI≥35kg/m2) was associated with a nearly 2-fold increase in mortality (HR 1.9, 95%CI 1.3-2.8). Higher leptin levels were associated with increased mortality after transplant surgery performed without cardiopulmonary bypass (p for interaction=0.03). A BMI≥30 kg/m2 was 26% sensitive and 97% specific for total body fat-defined obesity. Conclusions: A BMI of 30.0-34.9kg/m2 is not associated with 1-year mortality after lung transplantation in the LAS era, perhaps due to its low sensitivity for obesity. The association between leptin and mortality suggests the need to validate alternative methods to measure obesity in candidates for lung transplantation. A BMI ≥30kg/m2 may no longer contraindicate lung transplantation.
    American Journal of Respiratory and Critical Care Medicine 09/2014; 190(9). DOI:10.1164/rccm.201405-0973OC · 11.99 Impact Factor
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    ABSTRACT: Biomarker studies for early detection of acute kidney injury (AKI) have been limited by nonselective testing and uncertainties in using small changes in serum creatinine as a reference standard. Here we examine the ability of urine L-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and kidney injury molecule-1 (KIM-1) to predict injury progression, dialysis, or death within 7 days in critically ill adults with early AKI. Of 152 patients with known baseline creatinine examined, 36 experienced the composite outcome. Urine L-FABP demonstrated an area under the receiver-operating characteristic curve (AUC-ROC) of 0.79 (95% confidence interval 0.70-0.86), which improved to 0.82 (95% confidence interval 0.75-0.90) when added to the clinical model (AUC-ROC of 0.74). Urine NGAL, IL-18, and KIM-1 had AUC-ROCs of 0.65, 0.64, and 0.62, respectively, but did not significantly improve discrimination of the clinical model. The category-free net reclassification index improved with urine L-FABP (total net reclassification index for nonevents 31.0%) and urine NGAL (total net reclassification index for events 33.3%). However, only urine L-FABP significantly improved the integrated discrimination index. Thus, modest early changes in serum creatinine can help target biomarker measurement for determining prognosis with urine L-FABP, providing independent and additive prognostic information when combined with clinical predictors.Kidney International advance online publication, 17 September 2014; doi:10.1038/ki.2014.301.
    Kidney International 09/2014; 87(3). DOI:10.1038/ki.2014.301 · 8.52 Impact Factor
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    ABSTRACT: Background Subphenotypes have been identified within heterogeneous diseases such as asthma and breast cancer, with important therapeutic implications. We assessed whether subphenotypes exist within acute respiratory distress syndrome (ARDS), another heterogeneous disorder. Methods We used data from two ARDS randomised controlled trials (ARMA trial and ALVEOLI trial), sponsored by the National Heart, Lung, and Blood Institute. We applied latent class modelling to identify subphenotypes using clinical and biological data. We modelled data from both studies independently. We then tested the association of subphenotypes with clinical outcomes in both cohorts and with the response to positive end-expiratory pressure (PEEP) in the ALVEOLI cohort. Findings We analysed data for 1022 patients: 473 in the ARMA cohort and 549 in the ALVEOLI cohort. Independent latent class models indicated that a two-class (ie, two subphenotype) model was the best fit for both cohorts. In both cohorts, we identified a hyperinflammatory subphenotype (phenotype 2) that was characterised by higher plasma concentrations of inflammatory biomarkers, a higher prevalence of vasopressor use, lower serum bicarbonate concentrations, and a higher prevalence of sepsis than phenotype 1. Participants in phenotype 2 had higher mortality and fewer ventilator-free days and organ failure-free days in both cohorts than did those in phenotype 1 (p<0·007 for all). In the ALVEOLI cohort, the effects of ventilation strategy (high PEEP vs low PEEP) on mortality, ventilator-free days and organ failure-free days differed by phenotype (p=0·049 for mortality, p=0·018 for ventilator-free days, p=0·003 for organ-failure-free days). Interpretation We have identified two subphenotypes within ARDS, one of which is categorised by more severe inflammation, shock, and metabolic acidosis and by worse clinical outcomes. Response to treatment in a randomised trial of PEEP strategies differed on the basis of subphenotype. Identification of ARDS subphenotypes might be useful in selecting patients for future clinical trials. Funding National Institutes of Health.
    The Lancet Respiratory Medicine 08/2014; 2(8). DOI:10.1016/S2213-2600(14)70097-9

Publication Stats

11k Citations
1,464.07 Total Impact Points

Institutions

  • 2002–2015
    • Vanderbilt University
      • • Division of Allergy, Pulmonary and Critical Care
      • • Department of Medicine
      • • Department of Pathology, Microbiology and Immunology
      Нашвилл, Michigan, United States
    • University of Utah
      Salt Lake City, Utah, United States
    • University of California, Los Angeles
      • Division of Pulmonary and Critical Care
      Los Angeles, California, United States
  • 2014
    • Rhode Island Hospital
      Providence, Rhode Island, United States
    • The Ohio State University
      Columbus, Ohio, United States
  • 2012
    • Duke University
      Durham, North Carolina, United States
  • 2011
    • University of Pennsylvania
      • Department of Medicine
      Filadelfia, Pennsylvania, United States
  • 1999–2011
    • University of California, San Francisco
      • • Cardiovascular Research Institute
      • • Department of Medicine
      • • Division of Hospital Medicine
      San Francisco, CA, United States
  • 2002–2008
    • University of Alabama at Birmingham
      • • Department of Medicine
      • • Department of Pediatrics
      Birmingham, AL, United States
  • 2001–2008
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 2007
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      Torrance, California, United States
    • Stanford University
      • Department of Medicine
      Palo Alto, California, United States
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2003–2007
    • Children's Hospital & Research Center Oakland
      Oakland, California, United States
    • Cardiovascular Research Foundation
      New York, New York, United States
  • 2006
    • Kanazawa Medical University
      • Department of Thoracic Surgery
      Kanazawa-shi, Ishikawa-ken, Japan
    • Tokyo Medical and Dental University
      • Department of Anesthesiology
      Edo, Tōkyō, Japan