Lorraine B Ware

Vanderbilt University, Nashville, Michigan, United States

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Publications (217)1251.47 Total impact

  • [Show abstract] [Hide abstract]
    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; · 11.04 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;
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    ABSTRACT: Although recipients of donor lungs from smokers have worse clinical outcomes, the underlying mechanisms are unknown. We tested the association between donor smoking and the degree of pulmonary edema (as estimated by lung weight), the rate of alveolar fluid clearance (AFC; measured by airspace instillation of 5% albumin) and biomarkers of lung epithelial injury and inflammation (bronchoalveolar lavage [BAL] surfactant protein-D (SP-D) and IL-8) in ex vivo lungs recovered from 298 organ donors. The extent of pulmonary edema was higher in current smokers (n = 127) compared to nonsmokers (median 408 g, interquartile range [IQR] 364–500 vs. 385 g, IQR 340–460, p = 0.009). Oxygenation at study enrollment was worse in current smokers versus nonsmokers (median PaO2/FiO2 214 mm Hg, IQR 126–323 vs. 266 mm Hg, IQR 154–370, p = 0.02). Current smokers with the highest exposure (≥20 pack years) had significantly lower rates of AFC, suggesting that the effects of cigarette smoke on alveolar epithelial fluid transport function may be dose related. BAL IL-8 was significantly higher in smokers while SP-D was lower. These findings indicate that chronic exposure to cigarette smoke has important effects on inflammation, gas exchange, lung epithelial function and lung fluid balance in the organ donor that could influence lung function in the lung transplant recipient.
    American Journal of Transplantation 08/2014; · 6.19 Impact Factor
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    ABSTRACT: Background Cell free hemoglobin (CFH) is a potent nitric oxide scavenger associated with poor outcomes in several diseases. Pulmonary arterial hypertension (PAH) is characterized by reduced nitric oxide availability. We hypothesized that CFH would be elevated in PAH and associate with hemodynamics and clinical outcomes. Methods We measured CFH in 200 consecutively evaluated patients with PAH, 16 unaffected bone morphogenetic receptor protein type II (BMPR2) mutation carriers, 19 healthy subjects, and 29 patients with pulmonary venous hypertension (PVH). CFH values were tested for association with hemodynamics, time to hospitalization, and death. ResultsCFH was elevated in PAH patients and BMPR2 carriers compared to healthy subjects and PVH (p ≤ 0.01 all comparisons). There were no differences in CFH across PAH subtypes. CFH modestly correlated with mean pulmonary artery pressure (rs = 0.16, p = 0.03), pulmonary vascular resistance (rs = 0.21, p = 0.01), and inversely with cardiac index (rs = -0.18, p = 0.02) in PAH patients. CFH was not associated with hemodynamic response to nitric oxide or death. Patients with the highest CFH levels had increased risk of PAH-related hospitalization when adjusted for age, gender, and PAH etiology (HR 1.69, 95% CI 1.08 - 2.66, p = 0.02). ConclusionsCFH is elevated in a PAH patients and BMPR2 carriers compared with healthy subjects and PVH patients. Elevated CFH levels are independently associated with an increased risk of hospitalization. Further study is required to understand the mechanism of CFH elevation and the potential pathologic contribution of CFH in PAH.
    Chest 06/2014; · 7.13 Impact Factor
  • American Journal of Respiratory and Critical Care Medicine 06/2014; 189(12):1564-7. · 11.04 Impact Factor
  • James M Walter, Jennifer Wilson, Lorraine B Ware
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    ABSTRACT: Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by alveolar flooding with protein-rich pulmonary edema fluid. Despite an improved understanding of ARDS pathogenesis, our ability to predict the development of ARDS and risk-stratify patients with the disease remains limited. Biomarkers may help identify patients at highest risk of developing ARDS, assess response to therapy, predict outcome, and optimize enrollment in clinical trials. This review begins with a general description of biomarker use in clinical medicine. We then review evidence that supports the value of various ARDS biomarkers organized by the cellular injury processes central to ARDS development: endothelial injury, epithelial injury, disordered inflammation and coagulation, fibrosis, and apoptosis. Finally, we summarize the growing contributions of genomic and proteomic research and suggest ways in which the field may evolve in the coming years.
    Expert Review of Respiratory Medicine 05/2014;
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    ABSTRACT: Understanding differences in gene expression that increase risk for pulmonary arterial hypertension (PAH) is essential to understanding the molecular basis for disease. Previous studies on patient samples were limited by either end-stage disease effects or by use of non-adherent cells which are not ideal to model vascular cells in vivo. These studies addressed the hypothesis that pathological processes associated with PAH may be identified via a genetic signature common across multiple cell types. Expression array experiments were initially conducted analyzing cell types at different stages of vascular differentiation (mesenchymal stromal and endothelial) derived from PAH patient specific induced pluripotent stem cells (iPS cells). Molecular pathways which were altered in the PAH cell lines were then compared to fibroblasts from 21 patients, including both idiopathic and heritable PAH. Wnt was identified as a target pathway and validated in vitro using primary patient mesenchymal and endothelial cells. Taken together, our data suggest that the molecular lesions that cause PAH are present in all cell types evaluated regardless of origin and that stimulation of the Wnt signaling pathway was a common molecular defect in both heritable and idiopathic PAH.
    American journal of physiology. Cell physiology. 05/2014;
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    ABSTRACT: Despite the widespread use of multiplex immunoassays, there are very few scientific reports that test the accuracy and reliability of a platform prior to publication of experimental data. Our laboratory has previously demonstrated the need for new assay platform validation prior to use of biologic samples from large studies in order to optimize sample handling and assay performance. In this study, our goal was to test the accuracy and reproducibility of an electrochemiluminescent multiplex immunoassay platform (Meso Scale Discovery, MSD®) and compare this platform to validated, singleplex immunoassays (R&D Systems®) using actual study subject (human plasma and mouse bronchoalveolar lavage fluid (BALF) and plasma) samples. We found that the MSD platform performed well on intra- and inter-assay comparisons, spike and recovery and cross-platform comparisons. The mean intra-assay CV% and range for MSD was 3.49 (0.0-10.4) for IL-6 and 2.04 (0.1-7.9) for IL-8. The correlation between values for identical samples measured on both MSD and R&D was R=0.97 for both analytes. The mouse MSD assay had a broader range of CV% with means ranging from 9.5-28.5 depending on the analyte. The range of mean CV% was similar for single plex ELISAs at 4.3-23.7 depending on the analyte. Regardless of species or sample type, CV% was more variable at lower protein concentrations. In conclusion, we validated a multiplex electrochemiluminscent assay system and found that it has superior test characteristics in human plasma compared to mouse BALF and plasma. Both human and MSD assays compared favorably to well-validated singleplex ELISA's.
    Journal of immunological methods 04/2014; · 2.35 Impact Factor
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    ABSTRACT: Rationale: The acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that can develop at various times after major trauma. Objective: To identify and characterize distinct phenotypes of ARDS after trauma based on timing of syndrome onset. Methods: Latent class analyses were used to identify patterns of ARDS onset in a cohort of critically ill trauma patients. Identified patterns were tested for associations with known ARDS risk factors and associations were externally validated at a separate institution. Eleven plasma biomarkers representing pathophysiologic domains were compared between identified patterns in the validation cohort. Main Results: Three patterns of ARDS were identified; class I (52%) early onset on day 1 or 2, class II (40%) onset on days 3 and 4, and class III (8%) later onset on days 4 and 5. Early onset ARDS was associated with higher Abbreviated Injury Scale (AIS) scores for the thorax (p<0.001), lower lowest systolic blood pressure (SBP) prior to ICU admission (p=0.003), and a greater red blood cell transfusion requirement during resuscitation (p=0.030). In the external validation cohort, early onset ARDS was also associated with a higher AIS thorax (p=0.001) and a lower lowest SBP prior to ICU enrollment (p=0.006). In addition, the early onset phenotype demonstrated higher plasma levels of soluble receptor for advanced glycation end-products and angiopoietin-2. Conclusions: Degree of hemorrhagic shock and severity of thoracic trauma are associated with an early onset phenotype of ARDS after major trauma. Lung injury biomarkers suggest a dominant alveolar-capillary barrier injury pattern in this phenotype.
    Annals of the American Thoracic Society. 04/2014;
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    ABSTRACT: Donor lung utilization rates are persistently low primarily due to donor lung dysfunction. We hypothesized that a treatment that enhances the resolution of pulmonary edema by stimulating the rate of alveolar fluid clearance would improve donor oxygenation and increase donor lung utilization. We conducted a randomized, blinded, placebo-controlled trial of aerosolized albuterol (5mg q4h) versus saline placebo during active donor management in 506 organ donors.The primary outcome was change in oxygenation arterial partial pressure of oxygen/fraction of inspired oxygen [PaO2/FiO2] from enrollment to organ procurement.The albuterol (n¼260) and placebo (n¼246)groups were well matched for age, gender, ethnicity,smoking, and cause of brain death. The change in PaO2/FiO2 from enrollment to organ procurement did not differ between treatment groups (p¼0.54) nor did donor lung utilization (albuterol 29% vs. placebo 32%,p¼0.44). Donors in the albuterol versus placebo groups were more likely to have the study drug dose reduced (13% vs. 1%, p<0.001) or stopped (8% vs. 0%,p<0.001) for tachycardia. In summary, treatment with high dose inhaled albuterol during the donor management period did not improve donor oxygenation or increase donor lung utilization but did cause tachycardia.High dose aerosolized albuterol should not be used in donors to enhance the resolution of pulmonary edema.
    American Journal of Transplantation 03/2014; 14(3):621-8. · 6.19 Impact Factor
  • David R Janz, Lorraine B Ware
    Critical care medicine 03/2014; 42(3):755-6. · 6.37 Impact Factor
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    ABSTRACT: The aim of this study was to determine the association between 25-hydroxyvitamin D (25-OHD) levels at the onset of critical illness and the development of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in patients with sepsis or trauma. We performed two nested case-control studies of 478 patients with sepsis and trauma with or without ALI/ARDS admitted to the medical, surgical and trauma ICUs of a tertiary-care center. Cases consisted of patients with either sepsis or trauma and ALI/ARDS; controls consisted of equivalent numbers of matched patients with either sepsis or trauma alone. We measured serum 25-OHD levels the morning after ICU admission and used multivariable regression to assess the relationship between 25-OHD and diagnosis of ALI/ARDS during the first four ICU days, controlling for age, gender, diabetes, smoking status and season. 25-OHD levels did not differ between cases with ALI/ARDS and controls in either the sepsis or trauma cohorts. Using a conditional logistic regression model, sepsis patients during the winter season with higher 25-OHD levels were more likely to develop acute lung injury (odds ratio 1.68, 95% confidence interval of 1.05 to 2.69, P = 0.03). This association did not hold for the trauma cohort in either season. Sepsis and trauma patients had a lower risk of hospital mortality at higher 25-OHD levels but neither relationship reached significance. Higher one-year mortality after trauma was associated with lower 25-OHD levels (HR 0.50, CI 0.35,0.72 P = 0.001). Serum 25-OHD measured early after admission to intensive care is not associated with the development of acute lung injury, hospital or one-year mortality in critically ill patients with sepsis although lower 25-OHD levels were associated with higher one-year mortality in patients with severe trauma.
    Annals of intensive care. 02/2014; 4(1):5.
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    ABSTRACT: The Lung Injury Score (LIS) remains a commonly utilized measure of lung injury severity though the additive value of LIS to predict ARDS outcomes over the recent Berlin definition of ARDS, which incorporates severity, is not known. We tested the association of LIS (in which scores range from 0 to 4, with higher scores indicating more severe lung injury) and its four components calculated on the day of ARDS diagnosis with ARDS morbidity and mortality in a large, multi-ICU cohort of patients with Berlin-defined ARDS. Receiver Operator Characteristic (ROC) curves were generated to compare the predictive validity of LIS for mortality to Berlin stages of severity (mild, moderate and severe). In 550 ARDS patients, a one-point increase in LIS was associated with 58% increased odds of in-hospital death (95% CI 14 to 219%, P = 0.006), a 7% reduction in ventilator-free days (95% CI 2 to 13%, P = 0.01), and, among patients surviving hospitalization, a 25% increase in days of mechanical ventilation (95% CI 9 to 43%, P = 0.001) and a 16% increase (95% CI 2 to 31%, P = 0.02) in the number of ICU days. However, the mean LIS was only 0.2 points higher (95% CI 0.1 to 0.3) among those who died compared to those who lived. Berlin stages of severity were highly correlated with LIS (Spearman's rho 0.72, P < 0.0001) and were also significantly associated with ARDS mortality and similar morbidity measures. The predictive validity of LIS for mortality was similar to Berlin stages of severity with an area under the curve of 0.58 compared to 0.60, respectively (P-value 0.49). In a large, multi-ICU cohort of patients with ARDS, both LIS and the Berlin definition severity stages were associated with increased in-hospital morbidity and mortality. However, predictive validity of both scores was marginal, and there was no additive value of LIS over Berlin. Although neither LIS nor the Berlin definition were designed to prognosticate outcomes, these findings suggest that the role of LIS in characterizing lung injury severity in the era of the Berlin definition ARDS may be limited.
    Annals of intensive care. 02/2014; 4(1):4.
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    ABSTRACT: The research on biomarkers has been limited in its effectiveness because biomarker levels can only be measured within the thresholds of assays and laboratory instruments, a challenge referred to as a detection limit (DL) problem. In this paper, we propose a Bayesian approach to the Cox proportional hazards model with explanatory variables subject to lower, upper, or interval DLs. We demonstrate that by formulating the time-to-event outcome using the Poisson density with counting process notation, implementing the proposed approach in the OpenBUGS and JAGS is straightforward. We have conducted extensive simulations to compare the proposed Bayesian approach to the other four commonly used methods and to evaluate its robustness with respect to the distribution assumption of the biomarkers. The proposed Bayesian approach and other methods were applied to an acute lung injury study, in which a panel of cytokine biomarkers was studied for the biomarkers' association with ventilation-free survival.
    International journal of statistics in medical research. 01/2014; 3(1):32-43.
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    ABSTRACT: Rationale: Biological pathways with significant genetic conservation across human populations have been implicated in the pathogenesis of primary graft dysfunction (PGD). The evaluation of the role of recipient genetic variation in PGD has thus far been limited to single, candidate gene analyses. Objective: We sought to identify genetic variants in lung transplant recipients that are responsible for increased risk of PGD using a two-phase large-scale genotyping approach. Methods: Phase 1 was a large-scale candidate gene association study of the multicenter, prospective Lung Transplant Outcomes Group cohort. Phase 2 included functional evaluation of selected variants and a bioinformatics screening of variants identified in phase 1. Main Result: After genetic data quality control, 680 lung transplant recipients were included in the analysis. In phase 1, seventeen variants were significantly associated with PGD, four of which were in the prostaglandin E2 family of genes. Among these were a coding variant in the gene encoding prostaglandin E2 synthase (PTGES2, p=9.3x10-5) resulting in an arginine to histidine substitution at amino acid position 298, and three variants in a block containing the 5' promoter and first intron of the PTGER4 gene (encoding prostaglandin E2 receptor subtype 4, all p<5x10-5). Functional evaluation in regulatory T-cells identified that rs4434423A in the PTGER4 gene was associated with differential suppressive function of regulatory T cells. Conclusions: Further research aimed at replication and additional functional insight into the role played by genetic variation in prostaglandin E2 synthetic and signaling pathways in PGD is warranted.
    American Journal of Respiratory and Critical Care Medicine 01/2014; · 11.04 Impact Factor
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    ABSTRACT: Advances in supportive care and ventilator management for acute respiratory distress syndrome (ARDS) have resulted in declines in short-term mortality, but risks of death after survival to hospital discharge have not been well described. Our objective was to quantify the difference between short-term and long-term mortality in ARDS and to identify risk factors for death and causes of death at 1 year among hospital survivors. This multi-intensive care unit, prospective cohort included patients with ARDS enrolled between January 2006 and February 2010. We determined the clinical characteristics associated with in-hospital and 1-year mortality among hospital survivors and utilized death certificate data to identify causes of death. Of 646 patients hospitalized with ARDS, mortality at 1 year was substantially higher (41 %, 95 % CI 37-45 %) than in-hospital mortality (24 %, 95 % CI 21-27 %), P < 0.0001. Among 493 patients who survived to hospital discharge, the 110 (22 %) who died in the subsequent year were older (P < 0.001) and more likely to have been discharged to a nursing home, other hospital, or hospice compared to patients alive at 1 year (P < 0.001). Important predictors of death among hospital survivors were comorbidities present at the time of ARDS, and not living at home prior to admission. ARDS-related measures of severity of illness did not emerge as independent predictors of mortality in hospital survivors. Despite improvements in short-term ARDS outcomes, 1-year mortality is high, mostly because of the large burden of comorbidities, which are prevalent in patients with ARDS.
    European Journal of Intensive Care Medicine 01/2014; · 5.17 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. 01/2014;
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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 01/2014; · 2.46 Impact Factor
  • David R. Janz, Lorraine B. Ware
    Clinics in Chest Medicine. 01/2014;
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    ABSTRACT: Inherent recipient factors, including pretransplant diagnosis, obesity and elevated pulmonary pressures, are established primary graft dysfunction (PGD) risks. We evaluated the relationship between preoperative lung injury biomarkers and PGD to gain further mechanistic insight in recipients. We performed a prospective cohort study of recipients in the Lung Transplant Outcomes Group enrolled between 2002 and 2010. Our primary outcome was Grade 3 PGD on Day 2 or 3. We measured preoperative plasma levels of five biomarkers (CC-16, sRAGE, ICAM-1, IL-8 and Protein C) that were previously associated with PGD when measured at the postoperative time point. We used multivariable logistic regression to adjust for potential confounders. Of 714 subjects, 130 (18%) developed PGD. Median CC-16 levels were elevated in subjects with PGD (10.1 vs. 6.0, p < 0.001). CC-16 was associated with PGD in nonidiopathic pulmonary fibrosis (non-IPF) subjects (OR for highest quartile of CC-16: 2.87, 95% CI: 1.37, 6.00, p = 0.005) but not in subjects with IPF (OR 1.38, 95% CI: 0.43, 4.45, p = 0.59). After adjustment, preoperative CC-16 levels remained associated with PGD (OR: 3.03, 95% CI: 1.26, 7.30, p = 0.013) in non-IPF subjects. Our study suggests the importance of preexisting airway epithelial injury in PGD. Markers of airway epithelial injury may be helpful in pretransplant risk stratification in specific recipients.
    American Journal of Transplantation 01/2014; · 6.19 Impact Factor

Publication Stats

8k Citations
1,251.47 Total Impact Points


  • 2002–2014
    • Vanderbilt University
      • • Division of Allergy, Pulmonary and Critical Care
      • • Department of Medicine
      Nashville, Michigan, United States
    • University of Utah
      Salt Lake City, Utah, United States
  • 2012–2013
    • University of Pennsylvania
      • Division of Pulmonary, Allergy and Critical Care
      Philadelphia, PA, United States
  • 2011
    • Louisiana State University Health Sciences Center New Orleans
      • Department of Medicine
      Baton Rouge, LA, United States
    • Fred Hutchinson Cancer Research Center
      • Division of Clinical Research
      Seattle, WA, United States
    • Columbia University
      • Department of Medicine
      New York City, NY, United States
  • 2008–2011
    • Hospital of the University of Pennsylvania
      • Division of Pulmonary Allergy and Critical Care
      Philadelphia, Pennsylvania, United States
    • University of Colorado
      • Department of Medicine
      Denver, CO, United States
    • Massachusetts General Hospital
      • Center for Immunology and Inflammatory Diseases
      Boston, MA, United States
  • 1998–2011
    • University of California, San Francisco
      • • Division of Hospital Medicine
      • • Cardiovascular Research Institute
      San Francisco, CA, United States
  • 2010
    • Seattle Children's Hospital
      Seattle, Washington, United States
  • 2009
    • Institute for Cardiovascular Diseases
      Socola, Iaşi, Romania
  • 2002–2008
    • University of Alabama at Birmingham
      • • Department of Medicine
      • • Department of Pediatrics
      Birmingham, AL, United States
  • 2007
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      Torrance, California, 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
  • 2005
    • CUNY Graduate Center
      New York City, New York, United States
  • 2004
    • Fudan University
      Shanghai, Shanghai Shi, China
  • 2002–2004
    • University of California, Los Angeles
      • Division of Pulmonary and Critical Care
      Los Angeles, CA, United States
  • 1999–2004
    • CSU Mentor
      • Department of Medicine
      Long Beach, California, United States
  • 2001
    • Johns Hopkins University
      Baltimore, Maryland, United States