Dr. Joseph Levitt specializes in the treatment of adult pulmonary diseases including COPD, asthma, bronchiectasis, chronic cough, sarcoidosis, and pulmonary infections. He has practiced pulmonary medicine for more than 10 years. In addition to outpatient pulmonary medicine, Dr. Levitt is a critical care intensivist with a specific research interest in the clinical management of the Acute Respiratory Distress Syndrome (ARDS).

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

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

  • 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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  • 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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  • Human Mesenchymal Stromal Cells For Acute Respiratory Distress Syndrome (START) Recruiting

    This was a Phase 2a, randomized, double-blind, placebo-controlled, multi-center trial to assess the safety and efficacy of a single dose of Allogeneic Bone Marrow-derived Human Mesenchymal Stromal Cells (hMSCs) infusion in patients with Acute Respiratory Distress Syndrome (ARDS).

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

    The primary hypothesis was that early aspirin administration will decrease the rate of developing acute lung injury during the first 7 days after presentation to the hospital.

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

    This study tested whether inhaled budesonide and formoterol were able to alleviate or prevent pulmonary injury when administered early in hospital course to the patients at risk for developing acute respiratory distress syndrome (ARDS). The FDA has approved many uses for budesonide and formoterol, including asthma and chronic obstructive pulmonary disease (COPD), but the use of these two drugs is experimental for ARDS.

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  • Reevaluation Of Systemic Early Neuromuscular Blockade Recruiting

    This study evaluates whether giving a neuromuscular blocker (skeletal muscle relaxant) to a patient with acute respiratory distress syndrome will improve survival. Half of the patients will receive a neuromuscular blocker for two days and in the other half the use of neuromuscular blockers will be discouraged .

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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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2018-19 Courses

Graduate and Fellowship Programs


All Publications

  • Effect of Titrating Positive End-Expiratory Pressure (PEEP) With an Esophageal Pressure-Guided Strategy vs an Empirical High PEEP-FIO2 Strategy on Death and Days Free From Mechanical Ventilation Among Patients With Acute Respiratory Distress Syndrome A Randomized Clinical Trial Beitler, J. R., Sarge, T., Banner-Goodspeed, V. M., Gong, M. N., Cook, D., Novack, V., Loring, S. H., Talmor, D., Loring, S., Banner-Goodspeed, V., Fish, E., Jinadasa, S., Ritz, R., Previtera, J., Lee, L., Clarke, F., Piraino, T., Levitt, J., Vojnik, R., Park, P., Brierley, K., Haas, C., Weirauch, A., Fan, E., Matte, A., Harris, R., Kone, M., Heard, S., Longtine, K., Lellouche, F., Bouchard, P., Rubinson, L., McGrain, J., Griesdale, D. G., Foster, D., Oeckler, R., Amsbaugh, A., Jimenez, E., Danesh, V., Slutsky, A. S., Hall, J., Hubmayr, R. D., Rubenfeld, G., Schoenfeld, D., EPVent-2 Study Grp AMER MEDICAL ASSOC. 2019: 846–57


    Adjusting positive end-expiratory pressure (PEEP) to offset pleural pressure might attenuate lung injury and improve patient outcomes in acute respiratory distress syndrome (ARDS).To determine whether PEEP titration guided by esophageal pressure (PES), an estimate of pleural pressure, was more effective than empirical high PEEP-fraction of inspired oxygen (Fio2) in moderate to severe ARDS.Phase 2 randomized clinical trial conducted at 14 hospitals in North America. Two hundred mechanically ventilated patients aged 16 years and older with moderate to severe ARDS (Pao2:Fio2 ≤200 mm Hg) were enrolled between October 31, 2012, and September 14, 2017; long-term follow-up was completed July 30, 2018.Participants were randomized to PES-guided PEEP (n = 102) or empirical high PEEP-Fio2 (n = 98). All participants received low tidal volumes.The primary outcome was a ranked composite score incorporating death and days free from mechanical ventilation among survivors through day 28. Prespecified secondary outcomes included 28-day mortality, days free from mechanical ventilation among survivors, and need for rescue therapy.Two hundred patients were enrolled (mean [SD] age, 56 [16] years; 46% female) and completed 28-day follow-up. The primary composite end point was not significantly different between treatment groups (probability of more favorable outcome with PES-guided PEEP: 49.6% [95% CI, 41.7% to 57.5%]; P = .92). At 28 days, 33 of 102 patients (32.4%) assigned to PES-guided PEEP and 30 of 98 patients (30.6%) assigned to empirical PEEP-Fio2 died (risk difference, 1.7% [95% CI, -11.1% to 14.6%]; P = .88). Days free from mechanical ventilation among survivors was not significantly different (median [interquartile range]: 22 [15-24] vs 21 [16.5-24] days; median difference, 0 [95% CI, -1 to 2] days; P = .85). Patients assigned to PES-guided PEEP were significantly less likely to receive rescue therapy (4/102 [3.9%] vs 12/98 [12.2%]; risk difference, -8.3% [95% CI, -15.8% to -0.8%]; P = .04). None of the 7 other prespecified secondary clinical end points were significantly different. Adverse events included gross barotrauma, which occurred in 6 patients with PES-guided PEEP and 5 patients with empirical PEEP-Fio2.Among patients with moderate to severe ARDS, PES-guided PEEP, compared with empirical high PEEP-Fio2, resulted in no significant difference in death and days free from mechanical ventilation. These findings do not support PES-guided PEEP titration in Identifier NCT01681225.

    View details for DOI 10.1001/jama.2019.0555

    View details for Web of Science ID 000460351600015

    View details for PubMedID 30776290

  • Relationship Between Laryngeal Sensation, Length of Intubation, and Aspiration in Patients with Acute Respiratory Failure. Dysphagia Borders, J. C., Fink, D., Levitt, J. E., McKeehan, J., McNally, E., Rubio, A., Scheel, R., Siner, J. M., Taborda, S. G., Vojnik, R., Warner, H., White, S. D., Langmore, S. E., Moss, M., Krisciunas, G. P. 2019


    Dysphagia is common in hospitalized patients post-extubation and associated with poor outcomes. Laryngeal sensation is critical for airway protection and safe swallowing. However, current understanding of the relationship between laryngeal sensation and aspiration in post-extubation populations is limited. Acute respiratory failure patients requiring intensive care unit admission and mechanical ventilation received a Flexible Endoscopic Evaluation of Swallowing (FEES) within 72h of extubation. Univariate and multivariable analyses were performed to examine the relationship between laryngeal sensation, length of intubation, and aspiration. Secondary outcomes included pharyngolaryngeal secretions, pneumonia, and diet recommendations. One-hundred and three patients met inclusion criteria. Fifty-one patients demonstrated an absent laryngeal adductor reflex (LAR). Altered laryngeal sensation correlated with the presence of secretions (p=0.004). There was a significant interaction between the LAR, aspiration, and duration of mechanical ventilation. Altered laryngeal sensation was significantly associated with aspiration on FEES only in patients with a shorter length of intubation (p=0.008). Patients with altered laryngeal sensation were prescribed significantly more restricted liquid (p=0.03) and solid (p=0.001) diets. No relationship was found between laryngeal sensation and pneumonia. There is a high prevalence of laryngeal sensory deficits in mechanically ventilated patients post-extubation. Altered laryngeal sensation was associated with secretions, aspiration, and modified diet recommendations especially in those patients with a shorter length of mechanical ventilation. These results demonstrate that laryngeal sensory abnormalities impact the development of post-extubation dysphagia.

    View details for PubMedID 30694412

  • Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial. The Lancet. Respiratory medicine Matthay, M. A., Calfee, C. S., Zhuo, H., Thompson, B. T., Wilson, J. G., Levitt, J. E., Rogers, A. J., Gotts, J. E., Wiener-Kronish, J. P., Bajwa, E. K., Donahoe, M. P., McVerry, B. J., Ortiz, L. A., Exline, M., Christman, J. W., Abbott, J., Delucchi, K. L., Caballero, L., McMillan, M., McKenna, D. H., Liu, K. D. 2018


    BACKGROUND: Treatment with bone-marrow-derived mesenchymal stromal cells (MSCs) has shown benefits in preclinical models of acute respiratory distress syndrome (ARDS). Safety has not been established for administration of MSCs in critically ill patients with ARDS. We did a phase 2a trial to assess safety after administration of MSCs to patients with moderate to severe ARDS.METHODS: We did a prospective, double-blind, multicentre, randomised trial to assess treatment with one intravenous dose of MSCs compared with placebo. We recruited ventilated patients with moderate to severe ARDS (ratio of partial pressure of oxygen to fractional inspired oxygen <27 kPa and positive end-expiratory pressure [PEEP] ≥8 cm H2O) in five university medical centres in the USA. Patients were randomly assigned 2:1 to receive either 10 * 106/kg predicted bodyweight MSCs or placebo, according to a computer-generated schedule with a variable block design and stratified by site. We excluded patients younger than 18 years, those with trauma or moderate to severe liver disease, and those who had received cancer treatment in the previous 2 years. The primary endpoint was safety and all analyses were done by intention to treat. We also measured biomarkers in plasma. MSC viability was tested in a post-hoc analysis. This trial is registered with, number NCT02097641.FINDINGS: From March 24, 2014, to Feb 9, 2017 we screened 1038 patients, of whom 60 were eligible for and received treatment. No patient experienced any of the predefined MSC-related haemodynamic or respiratory adverse events. One patient in the MSC group died within 24 h of MSC infusion, but death was judged to be probably unrelated. 28-day mortality did not differ between the groups (30% in the MSC group vs 15% in the placebo group, odds ratio 2·4, 95% CI 0·5-15·1). At baseline, the MSC group had numerically higher mean scores than the placebo group for Acute Physiology and Chronic Health Evaluation III (APACHE III; 104 [SD 31] vs 89 [33]), minute ventilation (11·1 [3·2] vs 9·6 [2·4] L/min), and PEEP (12·4 [3·7] vs 10·8 [2·6] cm H2O). After adjustment for APACHE III score, the hazard ratio for mortality at 28 days was 1·43 (95% CI 0·40-5·12, p=0·58). Viability of MSCs ranged from 36% to 85%.INTERPRETATION: One dose of intravenous MSCs was safe in patients with moderate to severe ARDS. Larger trials are needed to assess efficacy, and the viability of MSCs must be improved.FUNDING: National Heart, Lung, and Blood Institute.

    View details for PubMedID 30455077

  • Randomized Clinical Trial of a Combination of an Inhaled Corticosteroid and Beta Agonist in Patients at Risk of Developing the Acute Respiratory Distress Syndrome CRITICAL CARE MEDICINE Festic, E., Carr, G. E., Cartin-Ceba, R., Hinds, R. F., Banner-Goodspeed, V., Bansal, V., Asuni, A. T., Talmor, D., Rajagopalan, G., Frank, R. D., Gajic, O., Matthay, M. A., Levitt, J. E. 2017; 45 (5): 798-805


    Effective pharmacologic treatments directly targeting lung injury in patients with the acute respiratory distress syndrome are lacking. Early treatment with inhaled corticosteroids and beta agonists may reduce progression to acute respiratory distress syndrome by reducing lung inflammation and enhancing alveolar fluid clearance.Double-blind, randomized clinical trial ( NCT01783821). The primary outcome was longitudinal change in oxygen saturation divided by the FIO2 (S/F) through day 5. We also analyzed categorical change in S/F by greater than 20%. Other outcomes included need for mechanical ventilation and development of acute respiratory distress syndrome.Five academic centers in the United States.Adult patients admitted through the emergency department at risk for acute respiratory distress syndrome.Aerosolized budesonide/formoterol versus placebo bid for up to 5 days.Sixty-one patients were enrolled from September 3, 2013, to June 9, 2015. Median time from presentation to first study drug was less than 9 hours. More patients in the control group had shock at enrollment (14 vs 3 patients). The longitudinal increase in S/F was greater in the treatment group (p = 0.02) and independent of shock (p = 0.04). Categorical change in S/F improved (p = 0.01) but not after adjustment for shock (p = 0.15). More patients in the placebo group developed acute respiratory distress syndrome (7 vs 0) and required mechanical ventilation (53% vs 21%).Early treatment with inhaled budesonide/formoterol in patients at risk for acute respiratory distress syndrome is feasible and improved oxygenation as assessed by S/F. These results support further study to test the efficacy of inhaled corticosteroids and beta agonists for prevention of acute respiratory distress syndrome.

    View details for DOI 10.1097/CCM.0000000000002284

    View details for Web of Science ID 000399522200007

    View details for PubMedID 28240689

  • Proteomic study of acute respiratory distress syndrome: current knowledge and implications for drug development EXPERT REVIEW OF PROTEOMICS Levitt, J. E., Rogers, A. J. 2016; 13 (5): 457-469


    The acute respiratory distress syndrome (ARDS) is a common cause of acute respiratory failure, and is associated with substantial mortality and morbidity. Dozens of clinical trials targeting ARDS have failed, with no drug specifically targeting lung injury in widespread clinical use. Thus, the need for drug development in ARDS is great. Targeted proteomic studies in ARDS have identified many key pathways in the disease, including inflammation, epithelial injury, endothelial injury or activation, and disordered coagulation and repair. Recent studies reveal the potential for proteomic changes to identify novel subphenotypes of ARDS patients who may be most likely to respond to therapy and could thus be targeted for enrollment in clinical trials. Nontargeted studies of proteomics in ARDS are just beginning and have the potential to identify novel drug targets and key pathways in the disease. Proteomics will play an important role in phenotyping of patients and developing novel therapies for ARDS in the future.

    View details for DOI 10.1586/14789450.2016.1172481

    View details for PubMedID 27031735

  • Increased Resource Use in Lung Transplant Admissions in the Lung Allocation Score Era AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Maxwelll, B. G., Mooney, J. J., Lee, P. H., Levitt, J. E., Chhatwani, L., Nicolls, M. R., Zamora, M. R., Valentine, V., Weill, D., Dhillon, G. S. 2015; 191 (3): 302-308


    Rationale: In 2005, the lung allocation score (LAS) was implemented to prioritize organ allocation to minimize waiting-list mortality and maximize one-year survival. It resulted in transplantation of older and sicker patients without changing one-year survival. Its effect on resource utilization is unknown. Objective: To determine changes in resource utilization over time in lung transplant admissions Methods: Solid organ transplant recipients were identified within the Nationwide Inpatient Sample (NIS) data from 2000 to 2011. Joinpoint regression methodology was performed to identify a time point of change in mean total hospital charges amongst lung transplant and other solid organ transplant recipients. Two temporal lung transplant recipient cohorts identified by joinpoint regression were compared for baseline characteristics and resource utilization, including total charges for index hospitalization, charges per day, length of stay, discharge disposition, tracheostomy, and need for extracorporeal membrane oxygenation (ECMO). Measurements and Main Results: A significant point of increased total hospital charges occurred for lung transplant recipients in 2005, corresponding to LAS implementation, that was not seen in other solid organ transplant recipients. Total transplant hospital charges increased by 40% in the post-LAS cohort [$569,942 ($53,229) vs. $407,489 ($28,360)] along with an increased median length of stay, daily charges, and discharge disposition other than to home. Post-LAS recipients also had higher post-transplant utilization of ECMO (OR 2.35, 95% CI 1.56, 3.55) and higher incidence of tracheostomy (OR 1.52, 95% CI 1.22, 1.89). Conclusions: LAS implementation is associated with a significant increase in resource utilization during index hospitalization for lung transplant.

    View details for DOI 10.1164/rccm.201408-1562OC

    View details for Web of Science ID 000348827000014

    View details for PubMedID 25517213

  • Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. The Lancet. Respiratory medicine Wilson, J. G., Liu, K. D., Zhuo, H., Caballero, L., McMillan, M., Fang, X., Cosgrove, K., Vojnik, R., Calfee, C. S., Lee, J., Rogers, A. J., Levitt, J., Wiener-Kronish, J., Bajwa, E. K., Leavitt, A., McKenna, D., Thompson, B. T., Matthay, M. A. 2015; 3 (1): 24-32


    No effective pharmacotherapy for acute respiratory distress syndrome (ARDS) exists, and mortality remains high. Preclinical studies support the efficacy of mesenchymal stem (stromal) cells (MSCs) in the treatment of lung injury. We aimed to test the safety of a single dose of allogeneic bone marrow-derived MSCs in patients with moderate-to-severe ARDS.The STem cells for ARDS Treatment (START) trial was a multicentre, open-label, dose-escalation, phase 1 clinical trial. Patients were enrolled in the intensive care units at University of California, San Francisco, CA, USA, Stanford University, Stanford, CA, USA, and Massachusetts General Hospital, Boston, MA, USA, between July 8, 2013, and Jan 13, 2014. Patients were included if they had moderate-to-severe ARDS as defined by the acute onset of the need for positive pressure ventilation by an endotracheal or tracheal tube, a PaO2:FiO2 less than 200 mm Hg with at least 8 cm H2O positive end-expiratory airway pressure (PEEP), and bilateral infiltrates consistent with pulmonary oedema on frontal chest radiograph. The first three patients were treated with low dose MSCs (1 million cells/kg predicted bodyweight [PBW]), the next three patients received intermediate dose MSCs (5 million cells/kg PBW), and the final three patients received high dose MSCs (10 million cells/kg PBW). Primary outcomes included the incidence of prespecified infusion-associated events and serious adverse events. The trial is registered with, number NCT01775774.No prespecified infusion-associated events or treatment-related adverse events were reported in any of the nine patients. Serious adverse events were subsequently noted in three patients during the weeks after the infusion: one patient died on study day 9, one patient died on study day 31, and one patient was discovered to have multiple embolic infarcts of the spleen, kidneys, and brain that were age-indeterminate, but thought to have occurred before the MSC infusion based on MRI results. None of these severe adverse events were thought to be MSC-related.A single intravenous infusion of allogeneic, bone marrow-derived human MSCs was well tolerated in nine patients with moderate to severe ARDS. Based on this phase 1 experience, we have proceeded to phase 2 testing of MSCs for moderate to severe ARDS with a primary focus on safety and secondary outcomes including respiratory, systemic, and biological endpoints.The National Heart, Lung, and Blood Institute.

    View details for DOI 10.1016/S2213-2600(14)70291-7

    View details for PubMedID 25529339

  • 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-?


    This article reviews the evolving definitions and epidemiology of the acute respiratory distress syndrome (ARDS) and highlights current efforts to improve identification of high-risk patients, thus to target prevention and early treatment before progression to ARDS. This information will be important for general practitioners and intensivists interested in improving the care of patients at risk for ARDS, and clinical researchers interested in designing clinical trials targeting the prevention and early treatment of acute lung injury.

    View details for DOI 10.1016/j.ccm.2014.08.002

    View details for Web of Science ID 000346214200002

  • 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): 609-624


    This article reviews the evolving definitions and epidemiology of the acute respiratory distress syndrome (ARDS) and highlights current efforts to improve identification of high-risk patients, thus to target prevention and early treatment before progression to ARDS. This information will be important for general practitioners and intensivists interested in improving the care of patients at risk for ARDS, and clinical researchers interested in designing clinical trials targeting the prevention and early treatment of acute lung injury.

    View details for DOI 10.1016/j.ccm.2014.08.002

    View details for PubMedID 25453413

  • Design and implementation of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of human mesenchymal stem/stromal cells for the treatment of moderate-severe acute respiratory distress syndrome ANNALS OF INTENSIVE CARE Liu, K. D., Wilson, J. G., Zhuo, H., Caballero, L., McMillan, M. L., Fang, X., Cosgrove, K., Calfee, C. S., Lee, J., Kangelaris, K. N., Gotts, J. E., Rogers, A. J., Levitt, J. E., Wiener-Kronish, J. P., Delucchi, K. L., Leavitt, A. D., McKenna, D. H., Thompson, B. T., Matthay, M. A. 2014; 4
  • 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

    View details for PubMedCentralID PMC3869104

  • Prehospital use of inhaled steroids and incidence of acute lung injury among patients at risk JOURNAL OF CRITICAL CARE Festic, E., Ortiz-Diaz, E., Lee, A., Li, G., Kor, D. J., Adebola, A., Akca, O., Hoth, J., Levitt, J. E., Carter, R., Gajic, O. 2013; 28 (6): 985-991


    Inhaled corticosteroids (ICSs) attenuated lung injury in animal studies. We investigated the association between prehospital ICS and incidence of acute lung injury (ALI) among patients at risk.In this ancillary analysis of the large multicenter Lung Injury Prediction Study cohort, we developed a propensity score for prehospital ICS use followed by matching, for all patients and for a subgroup of patients with at least 1 risk factor for direct pulmonary injury. The primary outcome was ALI; secondary outcomes included acute respiratory distress syndrome, need for invasive mechanical ventilation, and hospital mortality.Of the 5126 patients, 401 (8%) were using ICS. Acute lung injury developed in 343 (7%). The unadjusted incidence of ALI was 4.7% vs 6.9% (P = .12) among those in ICS compared with non-ICS group. In the "direct" lung injury subgroup, the unadjusted incidence of ALI was 4.1% vs 10.6% (P = 0.006). After propensity matching, the estimated effect for ALI in the whole cohort was 0.69 (95% confidence interval, 0.39-1.2; P = .18), and that in the direct subgroup was 0.56 (95% confidence interval, 0.22-1.46; P = .24).Preadmission use of ICS in a hospitalized population of patients at risk for ALI was not significantly associated with a lower incidence of ALI once controlled by comprehensive propensity-matched analysis.

    View details for DOI 10.1016/j.jcrc.2013.08.011

    View details for Web of Science ID 000326945100020

    View details for PubMedID 24075297

    View details for PubMedCentralID PMC4219561

  • 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 PubMedID 23782966

  • Emerging Pharmacological Therapies for Prevention and Early Treatment of Acute Lung Injury SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE Ortiz-Diaz, E., Festic, E., Gajic, O., Levitt, J. E. 2013; 34 (4): 448-458


    Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are serious complications of acute illness and injury, associated with an inpatient mortality of up to 40%. Despite considerable basic science and clinical research, therapeutic options for established ALI are limited. Survivors of ARDS are often faced with poor health-related quality of life, depressive-anxiety disorders, cognitive deficits, and financial strain. An attractive approach toward managing ALI lies in its prevention and early treatment. In addition to improving recognition of at-risk patients, it is necessary to identify novel treatments targeting the pathways that may prevent or ameliorate lung injury. The rationale and animal and clinical evidence for aspirin, systemic and inhaled steroids, β-agonists, renin-angiotensin axis blockers, statins, peroxisome proliferator agonist receptor ligands, curcumin, and inhaled heparin are included in this narrative review. Randomized, controlled trials are currently being designed and implemented to address their efficacy in populations at risk for ALI.

    View details for DOI 10.1055/s-0033-1351118

    View details for Web of Science ID 000322911200003

    View details for PubMedID 23934714

  • 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

    View details for PubMedCentralID PMC3469636

  • 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

    View details for PubMedCentralID PMC3580596

  • Clarithromycin for prevention of bronchiolitis obliterans syndrome in lung allograft recipients CLINICAL TRANSPLANTATION Dhillon, G. S., Valentine, V. G., Levitt, J., Patel, P., Gupta, M. R., Duncan, S. R., Seoane, L., Weill, D. 2012; 26 (1): 105-110


    Bronchiolitis obliterans syndrome (BOS) is the major limitation to long-term survival following lung transplantation and strategies to reduce its incidence have remained elusive. Macrolides may stabilize lung function in patients with established BOS. Their role, however, in prevention of BOS remains unexamined.Survival and BOS-free survival of 102 lung allograft recipients (LARs), transplanted at a single center between July 1995 and December 2001 who routinely received clarithromycin, were compared with two different control groups. The first control group consisted of 44 LARs from the same center who were transplanted from January 2002 onwards and did not receive clarithromycin. The second control group consisted of a contemporaneous cohort of 5089 recipients, transplanted between 1995 and 2001, reported to the United Network for Organ Sharing database.When compared with the first control group, BOS-free survival was reduced in LARs receiving clarithromycin. Univariate (hazard ratio [HR] 3.13, p-value = 0.004) and multivariate (HR 3.49, p-value = 0.04) analyses showed that routine use of clarithromycin was associated with an increased risk of developing BOS. When compared with the second control group, the five-yr survival of clarithromycin group was similar (p-value = 0.24).Routine use of clarithromycin does not delay development of BOS or improve survival.

    View details for DOI 10.1111/j.1399-0012.2011.01420.x

    View details for Web of Science ID 000300715100025

    View details for PubMedID 21352378

  • 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

    View details for PubMedCentralID PMC3044497

  • Impact of Hepatitis B Core Antibody Positive Donors in Lung and Heart-Lung Transplantation: An Analysis of the United Network for Organ Sharing Database TRANSPLANTATION Dhillon, G. S., Levitt, J., Mallidi, H., Valentine, V. G., Gupta, M. R., Sista, R., Weill, D. 2009; 88 (6): 842-846


    The availability of suitable lung and heart-lung allografts for transplantation remains poor. Accepting organs from donors with positive serological studies for hepatitis B could potentially expand the donor pool. The aim of this study was to assess the impact of donor hepatitis B core antibody (HBcAb) status on outcomes of lung and heart-lung transplant recipients.Using United Network for Organ Sharing/Organ Procurement and Transplantation Network data, we compared outcomes of 13,233 recipients of HBcAb negative organs with 333 recipients of HBcAb positive donor organs.We found that the unadjusted 1-year survival of recipients of HBcAb positive donor was worse, but there was no difference in survival after adjusting for baseline donor and recipient differences. On multivariate analysis, recipient and donor age, procedure type, era of transplant, baseline medical condition, diagnosis, and donor hepatitis C antibody status impacted 1- and 5-year survival. However, donor HBcAb status did not impact 1- or 5-year survival posttransplant.Lung and heart-lung allografts from HBcAb positive donors may be safely used, which would increase the number of transplants performed without compromising recipient outcomes.

    View details for DOI 10.1097/TP.0b013e3181b4e1fd

    View details for Web of Science ID 000270270500016

    View details for PubMedID 19920785

  • Does Itraconazole Improve Quality of Life in Severe Asthma with Fungal Sensitization? AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Khazeni, N., Levitt, J. E. 2009; 180 (2): 191-192

    View details for Web of Science ID 000268112500021

    View details for PubMedID 19578143

  • 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

    View details for PubMedCentralID PMC2758305

  • 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

    View details for PubMedCentralID PMC2542435

  • 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

    View details for PubMedCentralID PMC2374600

  • 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

  • Poor choice of primary outcome in a clinical trial of pirfenidone in patients with IPF AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LEVITT, J., Gould, M. K. 2005; 172 (9): 1228-1229

    View details for Web of Science ID 000232971400019

    View details for PubMedID 16249322