Keith M Wille

University of Alabama, Tuscaloosa, Alabama, United States

Are you Keith M Wille?

Claim your profile

Publications (71)361.54 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Pulmonary veno-occlusive disease (PVOD) is an uncommon cause of pulmonary arterial hypertension (PAH). However, unlike PAH, treatment options for PVOD are usually quite limited. The impact of the lung allocation score on access to transplantation for PVOD patients, and the clinical course of these patients, have not been well-described. Methods: Patients with a diagnosis of PVOD and PAH registered on the United Network for Organ Sharing wait list for transplantation from May 4, 2005-May 3, 2013 were included. Lung transplantation was the primary outcome measure. Multivariable analyses were performed to determine the odds of dying or receiving a lung transplant after listing. Survival was compared using Kaplan-Meier and competing risks methods. Results: Of 12,251 patients listed for lung transplantation, 49 with PVOD and 647 with PAH were identified. There were no significant differences in the lung allocation score between PVOD and PAH patients at listing, transplant, or wait list removal for death/ too sick for transplant. By 6 months, 22.6% of PVOD patients had been removed from the wait list due to death, compared to 11.0% of PAH patients (Chi square p=0.03). PVOD patients who died or were considered too sick for transplant were removed from the waiting list sooner after listing (22 vs. 105 days, p=0.08). There was no difference in the proportion of PVOD and PAH patients transplanted (50.0% vs. 47.6%, p=0.60). Conclusion: In the lung allocation score era, PVOD patients may be at higher risk for death while on the transplant waiting list. After wait list registration, close monitoring for disease progression is advised.
    Annals of the American Thoracic Society. 10/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Donor to recipient lung size matching at lung transplantation (LTx) can be estimated by the predicted total lung capacity (pTLC)ratio (donor pTLC/recipient pTLC). We aimed to determine whether the pTLC-ratio is associated with the risk of primary graft dysfunction (PGD) after bilateral LTx (BLT). Methods We calculated the pTLC-ratio for 812 adult BLTs from the Lung Transplant Outcomes Group between 3/2002-12/2010. Patients were stratified by pTLC-ratio>1.0 ("oversized") and pTLC-ratio≤1.0 ("undersized"). PGD was defined as any ISHLT grade 3 PGD within 72 hours of reperfusion (PGD 3). We analyzed the association between risk factors and PGD using multivariable conditional logistic regression. As transplant diagnoses can influence the size matching decisions and also modulate the risk for PGD, we performed pre-specified analyses by assessing the impact of lung size mismatch within diagnostic categories. Results In univariate analyses oversizing was associated with a 39% lower odds of PGD3 (OR 0.61, 95% CI, p=0.003). In a multivariate model accounting for center effects and known PGD risks, oversizing remained independently associated with a decreased odds of PGD3 (OR 0.58, 95% CI 0.38-0.88, p=0.01). The risk adjusted point estimate was similar for the non-COPD diagnoses groups (OR 0.52, 95%CI 0.32-0.86, p=0.01); however there was no detected association within the COPD group (OR 0.72, 95% CI 0.29-1.78, p=0.5). Conclusion Oversized allografts are associated with a decreased risk of PGD3 after BLT; this effect appears most apparent in non-COPD patients.
    The Journal of Heart and Lung Transplantation 09/2014; · 5.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Extracorporeal membrane oxygenation (ECMO) use during pregnancy and the post-partum period is thought to be associated with an increased risk for maternal or fetal bleeding complications. We present our recent institutional experience in managing pregnant and post-partum patients with ECMO. We also performed a literature review of modern use of ECMO in pregnant and post-partum patients utilizing Pubmed and Embase databases. ECMO was used for severe cardiopulmonary failure due to multiple conditions. Based on published reports, overall maternal and fetal survival on ECMO were 80% and 70%, respectively. Mild to moderate vaginal bleeding was reported in a few cases, with rare occurrences of catastrophic post-partum hemorrhage. There was no consensus on an optimal anticoagulation strategy in these patients, though most preferred to keep anticoagulation at lower therapeutic levels. We conclude that ECMO, in well-selected pregnant and post-partum patients, appears to be safe and associated with low risk of maternal and fetal complications.
    ASAIO journal (American Society for Artificial Internal Organs: 1992) 09/2014; · 1.39 Impact Factor
  • Source
    Transfusion 07/2014; 54(7). · 3.57 Impact Factor
  • American Journal of Respiratory and Critical Care Medicine 06/2014; 189(12):1564-7. · 11.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Regional citrate anticoagulation (RCA) is used as an anticoagulant for continuous renal replacement therapy (CRRT). A systemic calcium (Ca2+) infusion is required to replace Ca2+ lost in the effluent. The shortage of intravenous Ca2+ in the United States has limited RCA use. We describe a continuous veno-venous hemofiltration (CVVH) protocol with RCA using 2.2% anticoagulant citrate dextrose formula-A (ACD-A) and a commercial dialysate containing Ca2+ 1.5 mmol/l (N × Stage) as post-filter replacement fluid (RF), without need for Ca2+ infusion. We prospectively evaluated five patients on CRRT who had at least three episodes of filter clotting within 24 h. Patients were switched to CVVH using ACD-A infused pre-blood pump and titrated to achieve a post-filter ionized calcium (iCa2+) level <0.5 mmol/l. The Ca2+ -containing dialysate was delivered post-filter as RF. Steady state mean serum chemistries were: Na+: 140.8 ± 2.3 meq/l, K+: 4.2 ± 0.4 meq/l, HCO3-: 30.9 ± 3.7 meq/l, pH: 7.42 ± 0.07, CO2: 47.9 ± 8.3 mmHg, total Ca2+: 8.08 ± 1.09 mg/dL. Post-filter iCa2+ ranged 0.27-0.36 mmol/l, and patient iCa2+ ranged 0.81-1.24 mmol/l. Mean post-filter RF rate: 3086 ± 164 ml/h, mean ACD-A rate: 298 ± 21 ml/h. Mean blood flow rate: 200 ± 17 ml/min, mean filtration fraction: 39.6 ± 7.2%. Mean effluent flow rate: 38.6 ± 6.7 ml/kg/h (range 28.7-55.8). Mean filter survival was 7 h without anticoagulation, compared to 42.6 h in the ACD-A group (p<0.0001). In this pilot study, CVVH using ACD-A for RCA and a Ca2+ -containing RF was safely and effectively used without a continuous Ca2+ infusion. This protocol is a promising solution for maintaining effective CRRT when intravenous calcium is in short supply.
    The International journal of artificial organs 04/2014; · 1.45 Impact Factor
  • Source
    Kurt Prins, Keith Wille, Ashita Tolwani
    Journal of the American College of Cardiology 04/2014; 63(12). · 15.34 Impact Factor
  • [Show abstract] [Hide abstract]
    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 02/2014; · 6.19 Impact Factor
  • [Show abstract] [Hide abstract]
    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
  • Source
    NDT Plus 01/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Guillain-Barré syndrome (GBS) has been described after solid organ and bone marrow transplantation mostly due to viral infections and possibly calcineurin inhibitors. Incidence after bone marrow transplant is 0.3-0.7%, though incidence in other transplants is not well known. We present the first description of tacrolimus associated GBS in lung transplant recipients in the English language literature. The pathophysiology of tacrolimus-induced polyneuropathy is not known, but some have hypothesized that tacrolimus induces an inflammatory phenomenon by differential effects on T cell subsets. Diagnosis of association may be challenging and requires high index of suspicion. The optimal treatment of GBS-associated with tacrolimus after lung transplantation is unknown, although drug discontinuation may result in improvement in some patients, while some reports suggest that the use of IVIG and/or plasmapheresis may be helpful and safe in organ transplant recipients with severe symptoms.
    Case reports in transplantation. 01/2014; 2014:685010.
  • American Journal of Respiratory and Critical Care Medicine 01/2014; 189(1):112-4. · 11.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: ABSTRACT RATIONALE Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity primarily driven by acute exacerbations. Relative pulmonary artery (PA) enlargement, defined as a PA to ascending aorta (A) diameter ratio greater than one (PA:A>1) identifies patients at increased risk for exacerbations. However, little is known about the correlation between PA:A, echocardiography, and invasive hemodynamics in COPD. METHODS A retrospective observational study of severe COPD patients being evaluated for lung transplantation at a single center between 2007 and 2011 was conducted. Clinical characteristics, CT scans, echocardiograms, and right heart catheterizations were reviewed. The PA diameter at the bifurcation and aorta diameter from the same CT image were measured. Linear and logistic regression were used to examine the relationships between PA:A by CT and PA systolic pressure by echocardiogram (PASP) with invasive hemodynamics. Receiver operating characteristic (ROC) analysis assessed the utility of the PA:A ratio and PASP in predicting resting pulmonary hypertension (PH) [mean pulmonary artery pressure (mPAP) >25mmHg]. RESULTS 60 patients with a mean predicted FEV1 of 27±12% were evaluated. CT-measured PA:A correlated linearly with mPAP after adjustment for multiple covariates (r=0.30; p=0.03), a finding not observed with PASP. In a multivariate logistic model, mPAP was independently associated with PA:A>1 (Odds Ratio 1.44; 95% Confidence Interval (CI), 1.02-2.04; p=0.04). PA:A>1 was 73% sensitive and 84% specific for identifying patients with resting PH [AUC 0.83 (95% CI, 0.72 to 0.93; p<0.001)] while PASP was not useful. CONCLUSIONS A PA:A ratio >1 on CT outperforms echocardiography for diagnosing resting PH in patients with severe COPD.
    Chest 10/2013; · 7.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: In May 2005, the Lung Allocation Score (LAS) became the primary method for determining allocation of lungs for organ transplantation for those at least 12 years of age in the United States. During the pre-LAS period, black patients were more likely than white patients to become too sick or die while awaiting transplant. The association between gender and lung transplant outcomes has not been widely studied. METHODS: Black and white patients aged ≥18 years registered on the United Network of Organ Sharing (UNOS) lung transplantation waiting list from January 1, 2000, to May 3, 2005 (pre-LAS, n = 8,765), and from May 4, 2005, to September 4, 2010 (LAS, n = 8,806), were included. Logistic regression analyses were based on smaller cohorts derived from patients listed in the first 2 years of each era (2,350 pre-LAS, and 2,446 LAS) to allow for follow-up time. Lung transplantation was the primary outcome measure. Multivariable analyses were performed within each interval to determine the odds that a patient would die or receive a lung transplant within 3 years of listing. RESULTS: In the pre-LAS era, black patients were more likely than white patients to become too sick for transplantation or die within 3 years of waiting list registration (43.8% vs 30.8%; odds ratio [OR], 1.84; p < 0.001). Race was not associated with death or becoming too sick while listed for transplantation in the LAS era (14.0% vs 13.3%; OR, 0.93; p = 0.74). Black patients were less likely to undergo transplantation in the pre-LAS era (56.3% vs 69.2%; OR, 0.54; p < 0.001) but not in the LAS era (86.0% vs 86.7%; OR, 1.07; p = 0.74). Women were more likely than men to die or become too sick for transplantation within 3 years of listing in the LAS era (16.1% vs 11.3%; OR, 1.58; p < 0.001) compared with the pre-LAS era (33.4% vs 30.7%; OR, 1.19; p = 0.08). CONCLUSION: Racial disparities in lung transplantation have decreased with the implementation of LAS as the method of organ allocation; however, gender disparities may have actually increased in the LAS era.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 04/2013; · 5.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose Donor to recipient lung size mismatch at lung transplantation (LTx) can be estimated by the predicted total lung capacity (pTLC) ratio (=donor pTLC/recipient pTLC). We aimed to determine if the pTLCratio is associated with the risk of primary graft dysfunction (PGD) after bilateral LTx (BLT). Methods and Materials The LTx Outcomes Group is a prospective cohort study of patients undergoing first LTx at 10 centers. The pTLCratio was calculated for all adult BLTs between 3/2002-2/2010. Patients were stratified by pTLCratio>1.0(oversized) and pTLCratio≤1.0(undersized). PGD was defined by any ISHLT grade 3 PGD within 72 hours of allograft reperfusion. Logistic regression (LR) was used to estimate odds ratios (OR) for the association of the pTLCratio and PGD. Potential confounders were selected into multivariable models based on plausible association with pTLCratio or PGD. LTx center effects were accounted for by conditional LR. Results PGD developed in 37.6% of the 311 undersized and in 27.1% of the 501 oversized patients (p=0.001), table. In a multivariate model accounting for diagnosis, center volume, LTx era, ischemic time, bypass, transfusions, pulmonary artery systolic pressure, BMI, age, donor smoking and tidal volume at reperfusion oversizing was associated with a decreased probability of PGD (HR0.60, 95%CI0.42-0.88, p=0.009). This association was somewhat attenuated after additional accounting for clustering within centers (OR 0.69, 95%CI 0.46-1.01, p=0.06). [figure 1] Conclusions A pTLCratio >1.0 appears to be associated with a decreased risk of PGD after BLT. An oversized allograft may operate at relatively smaller tidal volumes and lower pulmonary vascular resistance, which could be a mechanistic link to PGD.
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S41. · 5.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Free hemoglobin (freeHgb) is a potent oxidant released from red cells in conditions such as sepsis, hemolysis, hemodialysis and cardiopulmonary bypass. We determined whether plasma freeHgb is elevated in lung transplant recipients and whether levels are associated with primary graft dysfunction (PGD). We also tested whether the potential oxidative injury associated with freeHgb is potentiated by high FiO2 at reperfusion.Methods and MaterialsPatients were lung recipients in the Lung Transplant Outcomes Group cohort and included 40 cases with Grade 3 PGD at 72h after transplant and 80 controls with no PGD, frequency matched for diagnosis (COPD, IPF) and procedure (single, bilateral). Plasma freeHgb was measured pre-op, and at 6 and 24h after reperfusion. PGD status was determined by ISHLT criteria.ResultsFreeHgb was detectable in 91% of pre-op, 97% of 6h and 85% of 24h samples. Pre-op [median 30 mg/dL (IQR 20-50 )] and 6h [30 (10-80)] levels were similar, but fell at 24h [20 (10-40), p=0.002]. Post-op freeHgb levels were similar between cases and controls although levels were higher in those who underwent cardiopulmonary bypass [80 (40–150) vs 20 (10–40), p<0.001]. By contrast, pre-op freeHgb levels were associated with PGD (p=0.043 for trend across freeHgb quartiles). In addition, pre-op freeHgb levels potentiated the association of high reperfusion FiO2 (≥0.40) with PGD (p=0.008, Figure).Conclusions High pre-op levels of plasma freeHgb associate with PGD, particularly when FiO2 is high at reperfusion. FreeHgb may be a mediator of oxidative injury during ischemia reperfusion and high levels of inspired O2 may potentiate this oxidative injury.
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S42-S43. · 5.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Primary graft dysfunction (PGD) is a complex phenotype secondary to multiple factors, including effects from many genes. We hypothesized plasma levels of plasminogen activator inhibitor-1 (PAI-1) could facilitate the discovery of SNPs important in PGD pathogenesis.Methods and MaterialsWe performed a nested case-control study within the multi-center Lung Transplant Outcomes Group cohort. Plasma PAI-1 levels were measured 24 hours post reperfusion. A SNP/protein association was tested in a linear model adjusted for recipient age, cardiopulmonary bypass, diagnosis, and population admixture using the 50K Illumina HumanCVD BeadChip v2. Significance cutoffs were set at p<5x10-4 for SNP/protein association and p<0.01 for validation. Additional, mediator analysis using logistic modeling with SNP and PAI-1 was performed to evaluate the nature of the effect between SNP, protein level and PGD.ResultsOf 1028 enrollees, 374 were evaluated for SNP/protein association and 654 used for validation. 42 SNPs met significance cutoffs for association; however, of those only rs3168046 and rs3793965 had minor allele frequencies greater than 5% and met our pre-specified significance. Both SNP’s encode Toll interacting protein (TOLLIP) and were in tight LD (R2=0.97). After adjusting for PAI-1 protein levels with PGD as response, PAI-1 plasma levels were demonstrated to mediate the candidate SNP PGD association.Conclusions Using PAI-1 as a quantitative trait for PGD can identify genetic variations which are important in PGD susceptibility. PAI-1 levels are associated with certain TOLLIP genotypes and may improve individual risk assessment based on innate immune function in lung transplant patients. Further studies examining these relationships are indicated.
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S29. · 5.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: ABSTRACT BACKGROUND: There is significant heterogeneity within the primary graft dysfunction (PGD) syndrome. We aimed to identify distinct grade 3 PGD phenotypes based on severity of lung dysfunction and patterns of resolution. METHODS: Subjects from the Lung Transplant Outcomes Group (LTOG) cohort study with grade 3 PGD within 72 hours after transplantation were included. Latent Class Analysis (LCA) was used to statistically identify classes based on changes in PGD ISHLT grade over time. Construct validity of the classes was assessed by testing for divergence of recipient, donor, and operative characteristics between classes. Predictive validity was assessed using time to death. RESULTS: 361 of 1255 subjects had grade 3 PGD within the first 72 hours after transplantation. LCA identified 3 distinct phenotypes: 1) severe persistent dysfunction (class 1); 2) complete resolution of dysfunction within 72 hours (class 2); and 3) attenuation, without complete resolution within 72 hours (class 3). Increased use of cardiopulmonary bypass, greater red blood cell transfusion and higher mean pulmonary artery pressure were associated with persistent PGD (class 1). Subjects in class 1 also had the greatest risk of death (HR 2.39, 95% CI: 1.57, 3.63, p<0.001). CONCLUSIONS: There are distinct phenotypes of resolution of dysfunction within the severe PGD syndrome. Subjects with early resolution may represent a different mechanism of lung pathology, such as resolving pulmonary edema, whereas classes with persistent PGD may represent a more severe phenotype. Future studies aimed at PGD mechanism or treatment may focus on phenotypes based on resolution of graft dysfunction.
    Chest 02/2013; · 7.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: RATIONALE: Primary graft dysfunction (PGD) is the main cause of early morbidity and mortality after lung transplantation. Previous studies have yielded conflicting results for PGD risk factors. OBJECTIVE: We sought to identify donor, recipient, and peri-operative risk factors for PGD. METHODS: We performed a 10 center prospective cohort study enrolled between March 2002 and December 2010 (the Lung Transplant Outcomes Group). The primary outcome was ISHLT grade 3 PGD at 48 or 72 hours post transplant. The association of potential risk factors with PGD was analyzed using multivariable conditional logistic regression. MEASUREMENTS AND MAIN RESULTS: 1255 patients from 10 centers were enrolled, 211 subjects (16.8%) developed grade 3 PGD. In multivariable models, independent risk factors for PGD were any history of donor smoking (OR=1.8, 95%CI 1.2, 2.6, p=0.002), FiO2 during allograft reperfusion (OR=1.1 per 10% increase in FiO2, 95%CI 1.0, 1.2; p=0.01), single lung transplant (OR=2.0, 95%CI 1.2, 3.3; p=0.008), use of cardiopulmonary bypass (OR=3.4, 95%CI 2.2, 5.3; p<0.001), overweight (OR=1.8, 95%CI 1.2, 2.7; p=0.01) and obese (OR=2.3, 95%CI 1.3, 3.9; p=0.004) recipient BMI, pre-operative sarcoidosis (OR=2.5, 95%CI 1.1, 5.6; p=0.03) or pulmonary arterial hypertension (OR=3.5, 95%CI 1.6, 7.7; p=0.002), and mean pulmonary artery pressure (OR=1.3 per 10mmHg increase, 95%CI 1.1, 1.5; p<0.001). PGD was significantly associated with 90 day (relative risk (RR)=4.8, absolute risk increase (ARI)=18%, p<0.001) and 1 year (RR=3.0, ARI=23%, p<0.001) mortality. Interpretation: We identified grade 3 PGD risk factors, several of which are potentially modifiable and should be prioritized for future research aimed at preventative strategies.
    American Journal of Respiratory and Critical Care Medicine 01/2013; · 11.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Primary graft dysfunction (PGD) is a significant contributor to early morbidity and mortality after lung transplantation. Increased vascular permeability in the allograft has been identified as a possible mechanism leading to PGD. Angiopoietin-2 serves as a partial antagonist to the Tie-2 receptor and induces increased endothelial permeability. We hypothesized that elevated Ang2 levels would be associated with development of PGD. We performed a case-control study, nested within the multi-center Lung Transplant Outcomes Group cohort. Plasma angiopoietin-2 levels were measured pre-transplant and 6 and 24 hours post-reperfusion. The primary outcome was development of grade 3 PGD in the first 72 hours. The association of angiopoietin-2 plasma levels and PGD was evaluated using generalized estimating equations (GEE). There were 40 PGD subjects and 79 non-PGD subjects included for analysis. Twenty-four PGD subjects (40%) and 47 non-PGD subjects (59%) received a transplant for the diagnosis of idiopathic pulmonary fibrosis (IPF). Among all subjects, GEE modeling identified a significant change in angiopoietin-2 level over time in cases compared to controls (p = 0.03). The association between change in angiopoietin-2 level over the perioperative time period was most significant in patients with a pre-operative diagnosis of IPF (p = 0.02); there was no statistically significant correlation between angiopoietin-2 plasma levels and the development of PGD in the subset of patients transplanted for chronic obstructive pulmonary disease (COPD) (p = 0.9). Angiopoietin-2 levels were significantly associated with the development of PGD after lung transplantation. Further studies examining the regulation of endothelial cell permeability in the pathogenesis of PGD are indicated.
    PLoS ONE 12/2012; 7(12):e51932. · 3.53 Impact Factor

Publication Stats

719 Citations
361.54 Total Impact Points


  • 2014
    • University of Alabama
      Tuscaloosa, Alabama, United States
  • 2004–2014
    • University of Alabama at Birmingham
      • • Division of Pulmonary, Allergy and Critical Care Medicine
      • • Department of Medicine
      Birmingham, Alabama, United States
  • 2011–2013
    • University of Pennsylvania
      • Division of Pulmonary, Allergy and Critical Care
      Philadelphia, PA, United States
    • Columbia University
      • Department of Medicine
      New York City, NY, United States
    • Stanford University
      • Division of Pulmonary and Critical Care Medicine
      Palo Alto, California, United States
  • 2008–2011
    • Hospital of the University of Pennsylvania
      • Division of Pulmonary Allergy and Critical Care
      Philadelphia, Pennsylvania, United States