Clinical Focus

  • Pulmonary Critical Care
  • Critical Care Medicine

Academic Appointments

Administrative Appointments

  • Program Director, Division of Pulmonary and Critical Care Medicine, Stanford University Department of Medicine (2015 - Present)

Professional Education

  • Board Certification: Critical Care Medicine, American Board of Internal Medicine (2006)
  • Residency:John H Stroger Jr Hospital of Cook County (2002) IL
  • Internship:University of Arizona (1999) AZ
  • Residency:University of Chicago Hospitals (2001) IL
  • Board Certification: Pulmonary Disease, American Board of Internal Medicine (2005)
  • Fellowship:Stanford University Medical Center (2005) CA
  • Fellowship:University of Chicago Hospitals (2004) IL
  • Medical Education:University of Minnesota School of Medicine (1998) MN
  • M.D., University of Minnesota (1998)

Research & Scholarship

Current Research and Scholarly Interests

My research focuses on the physiolgogic and biomarker characteristics of early acute lung injury (ALI) prior to need for mechanical ventilation. While, to date no pharmacologic treatment has improved survival in ALI, following the paradigm of early goal directed therapy for severe sepsis, clinical benefit may derive from identifying patients and initiating treatment prior to the need for positive pressure ventilation (and therefore prior to meeting current study entry criteria).

Clinical Trials

  • LIPS-B: Lung Injury Prevention Study With Budesonide and Beta Recruiting


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  • LIPS-A: Lung Injury Prevention Study With Aspirin Recruiting

    This is a multi-center, phase, phase II double-blind, placebo-controled, randomized trial of aspirin for the prevention of acute lung injury in patients identified as at risk for acute lung injury.

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  • EPVent 2- A Phase II Study of Mechanical Ventilation Directed by Transpulmonary Pressures Recruiting

    This phase II multi-centered, randomized controlled trial of mechanical ventilation directed by esophageal pressure measurement will test the primary hypothesis that using a strategy of maintaining a minimal but positive transpulmonary pressure (PTP = airway pressure minus pleural pressure) throughout the ventilatory cycle will lead to an improvement in patient survival.

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  • Statins for Acutely Injured Lungs From Sepsis Recruiting

    Objective: assess the efficacy and safety of oral rosuvastatin in patients with sepsis-induced Acute Lung Injury (ALI). Hypothesis: Rosuvastatin therapy will improve mortality in patients with sepsis-induced ALI.

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  • Human Mesenchymal Stem Cells For Acute Respiratory Distress Syndrome Recruiting

    This is a Phase 1, open label, dose escalation, multi-center clinical trial of Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells (hMSCs) for the treatment of Acute Respiratory Distress Syndrome (ARDS). The purpose of this study is to assess the safety of hMSCs in patients with ARDS.

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Graduate and Fellowship Programs


All Publications

  • Evolving Epidemiology and Definitions of the Acute Respiratory Distress Syndrome and Early Acute Lung Injury CLINICS IN CHEST MEDICINE Sweatt, A. J., Levitt, J. E. 2014; 35 (4): 609-?
  • Designing a better "nest": applicable to preventing hospital exposures to risk factors for acute respiratory distress syndrome or just retrospective study design? Critical care medicine Levitt, J. 2014; 42 (1): 197-198

    View details for DOI 10.1097/CCM.0b013e3182a11eab

    View details for PubMedID 24346523

  • Early Acute Lung Injury: Criteria for Identifying Lung Injury Prior to the Need for Positive Pressure Ventilation CRITICAL CARE MEDICINE Levitt, J. E., Calfee, C. S., Goldstein, B. A., Vojnik, R., Matthay, M. A. 2013; 41 (8): 1929-1937


    Mortality associated with acute lung injury remains high. Early identification of acute lung injury prior to onset of respiratory failure may provide a therapeutic window to target in future clinical trials. The recently validated Lung Injury Prediction Score identifies patients at risk for acute lung injury but may be limited for routine clinical use. We sought to empirically derive clinical criteria for a pragmatic definition of early acute lung injury to identify patients with lung injury prior to the need for positive pressure ventilation.Prospective observational cohort study.Stanford University Hospital.We prospectively evaluated 256 patients admitted to Stanford University Hospital with bilateral opacities on chest radiograph without isolated left atrial hypertension.None.Of the 256 patients enrolled, 62 patients (25%) progressed to acute lung injury requiring positive pressure ventilation. Clinical variables (through first 72 hr or up to 6 hr prior to acute lung injury) associated with progression to acute lung injury were analyzed by backward regression. Oxygen requirement, maximal respiratory rate, and baseline immune suppression were independent predictors of progression to acute lung injury. A simple three-component early acute lung injury score (1 point for oxygen requirement > 2-6 L/min or 2 points for > 6 L/min; 1 point each for a respiratory rate ≥ 30 and immune suppression) accurately identified patients who progressed to acute lung injury requiring positive pressure ventilation (area under the receiver-operator characteristic curve, 0.86) and performed similarly to the Lung Injury Prediction Score. An early acute lung injury score greater than or equal to 2 identified patients who progressed to acute lung injury with 89% sensitivity and 75% specificity. Median time of progression from early acute lung injury criteria to acute lung injury requiring positive pressure ventilation was 20 hours.This pragmatic definition of early acute lung injury accurately identified patients who progressed to acute lung injury prior to requiring positive pressure ventilation. Pending further validation, these criteria could be useful for future clinical trials targeting early treatment of acute lung injury.

    View details for DOI 10.1097/CCM.0b013e31828a3d99

    View details for Web of Science ID 000325701500027

    View details for PubMedID 23782966

  • Pathogenetic and predictive value of biomarkers in patients with ALI and lower severity of illness: results from two clinical trials AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY Agrawal, A., Zhuo, H., Brady, S., Levitt, J., Steingrub, J., Siegel, M. D., Soto, G., Peterson, M. W., Chesnutt, M. S., Matthay, M. A., Liu, K. D. 2012; 303 (8): L634-L639


    Plasma and bronchoalveolar lavage (BAL) biomarkers related to the pathogenesis of acute lung injury (ALI) have previously been associated with poorer clinical outcomes and increased disease severity among patients with ALI. Whether these biomarkers have predictive value in a less severely ill population that excludes septic patients with high APACHE II scores is currently unknown. We tested the association of plasma and BAL biomarkers with physiological markers of ALI severity or clinically relevant outcomes in a secondary analysis of a clinical trial of activated protein C for the treatment of ALI. Plasma plasminogen activator inhibitor-1 (PAI-1) and mini-BAL protein were both significantly associated with increased oxygenation index (P = 0.02 and 0.01, respectively), whereas there was a trend toward an association between IL-6 and oxygenation index (P = 0.057). High plasma IL-6, thrombomodulin, and mini-BAL protein were all significantly associated with fewer ventilator-free days (VFDs) (P = 0.01, 0.01, and 0.05, respectively); no markers were associated with mortality, but we hypothesized that this was due to the small size of our cohort and the low death rate. To confirm these associations in a larger sample, we identified a restricted cohort of patients from the ARDS Network ALVEOLI study with similar baseline characteristics. We retested the associations of the significant biomarkers with markers of severity and clinical outcomes and studied IL-8 as an additional biomarker given its important predictive value in prior studies. In this restricted cohort, IL-6 was significantly associated with oxygenation index (P = 0.02). Both IL-6 and IL-8 were associated with decreased VFDs and increased 28-day mortality. Future studies should be focused on examining larger numbers of patients with less severe ALI to further test the relative predictive value of plasma and mini-BAL biomarkers for clinically relevant outcomes, including VFDs and mortality, and for their prospective utility in risk stratification for future clinical trials.

    View details for DOI 10.1152/ajplung.00195.2012

    View details for Web of Science ID 000309996300002

    View details for PubMedID 22865551

  • Clinical review: Early treatment of acute lung injury - paradigm shift toward prevention and treatment prior to respiratory failure CRITICAL CARE Levitt, J. E., Matthay, M. A. 2012; 16 (3)


    ABSTRACT: Acute lung injury (ALI) remains a major cause of morbidity and mortality in critically ill patients. Despite improved understanding of the pathogenesis of ALI, supportive care with a lung protective strategy of mechanical ventilation remains the only treatment with a proven survival advantage. Most clinical trials in ALI have targeted mechanically ventilated patients. Past trials of pharmacologic agents may have failed to demonstrate efficacy in part due to the resultant delay in initiation of therapy until several days after the onset of lung injury. Improved early identification of at-risk patients provides new opportunities for risk factor modification to prevent the development of ALI and novel patient groups to target for early treatment of ALI before progression to the need for mechanical ventilation. This review will discuss current strategies that target prevention of ALI and some of the most promising pharmacologic agents for early treatment of ALI prior to the onset of respiratory failure that requires mechanical ventilation.

    View details for DOI 10.1186/cc11144

    View details for Web of Science ID 000313197500058

    View details for PubMedID 22713281

  • PATIENT-RELATED FACTORS ASSOCIATED WITH HOSPITAL DISCHARGE TO A CARE FACILITY AFTER CRITICAL ILLNESS AMERICAN JOURNAL OF CRITICAL CARE Gehlbach, B. K., Salamanca, V. R., Levitt, J. E., Sachs, G. A., Sweeney, M. K., Pohlman, A. S., Charbeneau, J., Krishnan, J. A., Hall, J. B. 2011; 20 (5): 378-386


    Many critically ill patients are transferred to other care facilities instead of to home at hospital discharge.To identify patient-related factors associated with hospital discharge to a care facility after critical illness and to estimate the magnitude of risk associated with each factor.Retrospective cohort study of 548 survivors of critical illness in a medical intensive care unit. Multivariable logistic regression was used to identify independent risk factors for discharge to a care facility. Only the first 72 hours of intensive care were analyzed.Approximately one-quarter of the survivors of critical illness were discharged to a care facility instead of to home. This event occurred more commonly in older patients, even after adjustment for severity of illness and comorbid conditions (odds ratio [OR] 1.8 for patients ? 65 years of age vs patients < 65 years; 95% confidence interval [CI], 1.1-3.1; P = .02). The risk was greatest for patients who received mechanical ventilation (OR, 3.4; 95% CI, 2.0-5.8; P < .001) or had hospitalizations characterized by severe cognitive dysfunction (OR, 8.1; 95% CI, 1.3-50.6; P = .02) or poor strength and/or mobility (OR, 31.7; 95% CI, 6.4-157.3; P < .001). The model showed good discrimination (area under the curve, 0.82; 95% CI, 0.77-0.86).The model, which did not include baseline function or social variables, provided good discrimination between patients discharged to a care facility after critical illness and patients discharged to home. These results suggest that future research should focus on the debilitating effects of respiratory failure and on conditions with cognitive and neuromuscular sequelae.

    View details for DOI 10.4037/ajcc2011827

    View details for Web of Science ID 000294460500006

    View details for PubMedID 21885459

  • The utility of clinical predictors of acute lung injury: towards prevention and earlier recognition. Expert review of respiratory medicine Levitt, J. E., Matthay, M. A. 2010; 4 (6): 785-797


    Despite significant advances in our understanding of the pathophysiology of acute lung injury, a lung-protective strategy of mechanical ventilation remains the only therapy with a proven survival advantage. Numerous pharmacologic therapies have failed to show benefit in multicenter clinical trials. The paradigm of early, goal-directed therapy of sepsis suggests greater clinical benefit may derive from initiating therapy prior to the onset of respiratory failure that requires mechanical ventilation. Thus, there is heightened interest in more accurate and complete characterization of high-risk patient populations and identification of patients in the early stage of acute lung injury, prior to the need for mechanical ventilation. This article discusses the growing literature on clinical predictors of acute lung injury (including risk factors for specific subgroups) with an emphasis on transfusion-related risk factors and recent research targeting the early identification of high-risk patients and those with early acute lung injury prior to the onset of respiratory failure.

    View details for DOI 10.1586/ers.10.78

    View details for PubMedID 21128753

  • The pathogenetic and prognostic value of biologic markers in acute lung injury. Journal of intensive care medicine Levitt, J. E., Gould, M. K., Ware, L. B., Matthay, M. A. 2009; 24 (3): 151-167


    Over the past 2 decades, measurement of biomarkers in both the airspaces and plasma early in the course of acute lung injury has provided new insights into the mechanisms of lung injury. In addition, biologic markers of cell-specific injury, acute inflammation, and altered coagulation correlate with mortality from acute lung injury in several single center studies as well as in multicenter clinical trials. To date, biomarkers have been measured largely for research purposes. However, with improved understanding of their role in the pathogenesis of acute lung injury, biomarkers may play an important role in early detection of lung injury, risk stratification for clinical trials, and, ultimately, tailoring specific therapies to individual patients. This article provides a review of biologic markers in acute lung injury, with an emphasis on recent analysis of results from multicenter clinical trials.

    View details for DOI 10.1177/0885066609332603

    View details for PubMedID 19282296

  • Identification of Early Acute Lung Injury at Initial Evaluation in an Acute Care Setting Prior to the Onset of Respiratory Failure CHEST Levitt, J. E., Bedi, H., Calfee, C. S., Gould, M. K., Matthay, M. A. 2009; 135 (4): 936-943


    Despite being a focus of intensive investigation, acute lung injury (ALI) remains a major cause of morbidity and mortality. However, the current consensus definition impedes identification of patients with ALI before they require mechanical ventilation. To establish a definition of early ALI (EALI), we carried out a prospective cohort study to identify clinical predictors of progression to ALI.Potential cases of EALI were identified by daily screening of chest radiographs (CXRs) for all adult emergency department and new medicine service admissions at Stanford University Hospital.Of 1,935 screened patients with abnormal CXRs, we enrolled 100 patients admitted with bilateral opacities present < 7 days and not due exclusively to left atrial hypertension. A total of 33 of these 100 patients progressed to ALI requiring mechanical ventilation during their hospitalization. Progression to ALI was associated with immunosuppression, the modified Rapid Emergency Medicine Score, airspace opacities beyond the bases, systemic inflammatory response syndrome, and the initial oxygen requirement (> 2 L/min). On multivariate analysis, only an initial oxygen requirement > 2 L/min predicted progression to ALI (odds ratio, 8.1; 95% confidence interval, 2.7 to 24.5). A clinical diagnosis of EALI, defined by hospital admission with bilateral opacities on CXR not exclusively due to left atrial hypertension and an initial oxygen requirement of > 2 L/min, was 73% sensitive and 79% specific for progression to ALI.A new clinical definition of EALI may have value in identifying patients with ALI early in their disease course.

    View details for DOI 10.1378/chest.08-2346

    View details for Web of Science ID 000265113800012

    View details for PubMedID 19188549

  • Randomized clinical trial of activated protein C for the treatment of acute lung injury AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Liu, K. D., Levitt, J., Zhuo, H., Kallet, R. H., Brady, S., Steingrub, J., Tidswell, M., Siegel, M. D., Soto, G., Peterson, M. W., Chesnutt, M. S., Phillips, C., Weinacker, A., Thompson, B. T., Eisner, M. D., Matthay, M. A. 2008; 178 (6): 618-623


    Microvascular injury, inflammation, and coagulation play critical roles in the pathogenesis of acute lung injury (ALI). Plasma protein C levels are decreased in patients with acute lung injury and are associated with higher mortality and fewer ventilator-free days.To test the efficacy of activated protein C (APC) as a therapy for patients with ALI.Eligible subjects were critically ill patients who met the American/European consensus criteria for ALI. Patients with severe sepsis and an APACHE II score of 25 or more were excluded. Participants were randomized to receive APC (24 microg/kg/h for 96 h) or placebo in a double-blind fashion within 72 hours of the onset of ALI. The primary endpoint was ventilator-free days.APC increased plasma protein C levels (P = 0.002) and decreased pulmonary dead space fraction (P = 0.02). However, there was no statistically significant difference between patients receiving placebo (n = 38) or APC (n = 37) in the number of ventilator-free days (median [25-75% interquartile range]: 19 [0-24] vs. 19 [14-22], respectively; P = 0.78) or in 60-day mortality (5/38 vs. 5/37 patients, respectively; P = 1.0). There were no differences in the number of bleeding events between the two groups.APC did not improve outcomes from ALI. The results of this trial do not support a large clinical trial of APC for ALI in the absence of severe sepsis and high disease severity.

    View details for DOI 10.1164/rccm.200803-419OC

    View details for Web of Science ID 000259158600011

    View details for PubMedID 18565951

  • Diagnostic utility of B-type natriuretic peptide in critically ill patients with pulmonary edema: a prospective cohort study CRITICAL CARE Levitt, J. E., Vinayak, A. G., Gehlbach, B. K., Pohlman, A., Van Cleve, W., Hall, J. B., Kress, J. P. 2008; 12 (1)


    Distinguishing pulmonary edema due to acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS) from hydrostatic or cardiogenic edema is challenging in critically ill patients. B-type natriuretic peptide (BNP) can effectively identify congestive heart failure in the emergency room setting but, despite increasing use, its diagnostic utility has not been validated in the intensive care unit (ICU).We performed a prospective, blinded cohort study in the medical and surgical ICUs at the University of Chicago Hospitals. Patients were eligible if they were admitted to the ICU with respiratory distress, bilateral pulmonary edema and a central venous catheter suggesting either high-pressure (cardiogenic) or low-pressure (ALI/ARDS) pulmonary edema. BNP levels were measured within 48 hours of ICU admission and development of pulmonary edema and onward up to three consecutive days. All levels were drawn simultaneously with the measurement of right atrial or pulmonary artery wedge pressure. The etiology of pulmonary edema--cardiogenic or ALI/ARDS--was determined by three intensivists blinded to BNP levels.We enrolled a total of 54 patients (33 with ALI/ARDS and 21 with cardiogenic edema). BNP levels were lower in patients with ALI/ARDS than in those with cardiogenic edema (496 +/- 439 versus 747 +/- 476 pg/ml, P = 0.05). At an accepted cutoff of 100 pg/ml, specificity for the diagnosis of ALI/ARDS was high (95.2%) but sensitivity was poor (27.3%). Cutoffs at higher BNP levels improved sensitivity at considerable cost to specificity. Invasive measures of filling pressures correlated poorly with initial BNP levels and subsequent day BNP values fluctuated unpredictably and without correlation with hemodynamic changes and net fluid balance.BNP levels drawn within 48 hours of admission to the ICU do not reliably distinguish ALI/ARDS from cardiogenic edema, do not correlate with invasive hemodynamic measurements, and do not track predictably with changes in volume status on consecutive daily measurements.

    View details for DOI 10.1186/cc6764

    View details for Web of Science ID 000254812500043

    View details for PubMedID 18194554

  • Daily sedative interruption in mechanically ventilated patients at risk for coronary artery disease CRITICAL CARE MEDICINE Kress, J. P., Vinayak, A. G., Levitt, J., Schweickert, W. D., Gehlbach, B. K., Zimmerman, F., Pohlman, A. S., Hall, J. B. 2007; 35 (2): 365-371


    To determine the prevalence of myocardial ischemia in mechanically ventilated patients with coronary risk factors and compare periods of sedative interruption vs. sedative infusion.Prospective, blinded observational study.Medical intensive care unit of tertiary care medical center.Intubated, mechanically ventilated patients with established coronary artery disease risk factors.Continuous three-lead Holter monitors with ST-segment analysis by a blinded cardiologist were used to detect myocardial ischemia. Ischemia was defined as ST-segment elevation or depression of >0.1 mV from baseline.Comparisons between periods of awakening from sedation vs. sedative infusion were made. Vital signs, catecholamine levels, and time with ischemia detected by Holter monitor during the two periods were compared. Heart rate, mean arterial pressure, rate-pressure product, respiratory rate, and catecholamine levels were all significantly higher during sedative interruption. Eighteen of 74 patients (24%) demonstrated ischemic changes. Patients with myocardial ischemia had a longer intensive care unit length of stay (17.4+/-17.5 vs. 9.6+/-6.7 days, p=.04). Despite changes in vital signs and catecholamine levels during sedative interruption, fraction of ischemic time did not differ between the time awake vs. time sedated [median [interquartile range] of 0% [0, 0] compared with 0% [0, 0] while they were sedated [p=.17]). The finding of similar fractions of ischemic time between awake and sedated states persisted with analysis of the subgroup of 18 patients with ischemia.Myocardial ischemia is common in critically ill mechanically ventilated patients with coronary artery disease risk factors. Daily sedative interruption is not associated with an increased occurrence of myocardial ischemia in these patients.

    View details for DOI 10.1097/01.CCM.0000254334.46406.B3

    View details for Web of Science ID 000243739100004

    View details for PubMedID 17205005

  • Usefulness of the external jugular vein examination in detecting abnormal central venous pressure in critically ill patients ARCHIVES OF INTERNAL MEDICINE Vinayak, A. G., Levitt, J., Gehlbach, B., Pohlman, A. S., Hall, J. B., Kress, J. P. 2006; 166 (19): 2132-2137


    Central venous pressure (CVP) provides important information for the management of critically ill patients. The external jugular vein (EJV) is easier to visualize than the internal jugular vein and may give a reliable estimate of CVP.To determine the usefulness of the EJV examination in detecting abnormal CVP values, we performed a prospective blinded evaluation comparing it with CVP measured using an indwelling catheter in critically ill patients with central venous catheters. Blinded EJV examinations were performed by clinicians with 3 experience levels (attending physicians, residents and fellows, and interns and fourth-year medical students) to estimate CVP (categorized as low [/=10 cm of water]). The usefulness of the EJV examination in discriminating low vs high CVP was measured using receiver operating characteristic curve analysis.One hundred eighteen observations were recorded among 35 patients. The range of CVP values was 2 to 20 cm of water. The EJV was easier to visualize than the internal jugular vein (mean visual analog scale score, 8 vs 5; P<.001). The reliability for determining low and high CVP was excellent, with areas under the curve of 0.95 (95% confidence interval [CI], 0.88-1.00) and 0.97 (95% CI, 0.92-1.00), respectively, for attending physicians and 0.86 (95% CI, 0.78-0.95) and 0.90 (95% CI, 0.84-0.96), respectively, for all examiners.The EJV examination correlates well with catheter-measured CVP and is a reliable means of identifying low and high CVP values.

    View details for Web of Science ID 000241467500010

    View details for PubMedID 17060544

  • Treatment of acute lung injury: Historical perspective and potential future therapies SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE Levitt, J. E., Matthay, M. A. 2006; 27 (4): 426-437


    The acute respiratory distress syndrome (ARDS) was first described by Ashbaugh and colleagues in 1967. However, despite considerable efforts, early progress in treatment was slowed by lack of consistent definitions and appropriately powered clinical trials. In 1994, the American-European Consensus Conference on ARDS established criteria defining ARDS as well as acute lung injury (ALI). Additionally, the conference established research directives and international coordination of clinical studies. Current incidence of ALI in the United States is estimated at 200,000 cases per year with a mortality rate approaching 40%. Mechanical ventilation, using positive end-expiratory pressure and reduced tidal volumes and inspiratory pressures, along with improved supportive care has increased survival rates. However, to date, pharmacological therapies have failed to improve survival in multicenter clinical trials. This article focuses on clinical treatments for ALI that have been tested in phase II and III clinical trials as well as a discussion of potential future therapies.

    View details for DOI 10.1055/s-2006-948296

    View details for Web of Science ID 000239897800011

    View details for PubMedID 16909376