TCV Lab

The research mission of the Division of  Thoracic Surgery is to create an environment in which new knowledge is generated that will advance the field and ultimately benefit our patients. Our Divisions have a long history of success in research and have contributed significantly to the medical literature. All faculty members are involved in various types of research including studying basic scientific questions related to diseases of the heart, chest, and blood vessels, as well as important clinical research questions related to improving outcomes for our patients. A few examples of the expertise of our faculty include:

• how aortic aneurysms form
• why transplanted lungs fail over time
• methods to improve heart function after heart attacks.

Our faculty has been very successful in obtaining extramural funding with many of our faculty members having NIH funding through the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI), or the Agency for Healthcare Research and Quality (AHRQ), or the Patient Centered Outcomes Research Institute (PCORI). This level of peer-reviewed extramural support puts our division on par with the most productive thoracic surgical groups around the country and demonstrates the commitment of our Division and our faculty to our research mission.

In addition to using our research programs to address clinical problems in our discipline, we also are keenly interested in creating opportunities for the training of students and residents in research techniques and strategies.

The TCV Lab had its origins over 35 years ago in the early 1980’s here at the University of Virginia. Dr. Irv Kron had come here as a TCV resident and found himself looking for ways to study clinical questions in a laboratory environment. He recruited some of the UVA general surgery residents to help with some of these projects, including Dr. Curt Tribble. The first successful project that this group of intrepid residents took on was one of the first studies of what was to become known as ‘the abdominal compartment syndrome’.   At first, these projects were done in off hours in the lab of one of the established investigators in the Department, Dr. Wallace Ritchie, who graciously allowed his lab space to be used for these studies.  Subsequent projects included looking at renal perfusion during sepsis and the spinal cord ischemia that can result from aortic cross-clamping.  Dr. Kron worked to get early funding for these efforts from the American Heart Association, industry (Gore, Merck, DuPont, etc), and various UVA related faculty development programs (Jeffress Foundation and a UVA based NIH funded R&D development award). Drs. Kron and Nolan helped support Dr. Tribble’s post-doctoral fellowship to study adenosine physiology and pharmacology in Dr. Robert Berne’s lab in the Department of Physiology prior to his return to the TCV lab.

The TCV lab’s first RO1 NIH grant was awarded in1992, with Dr. Kron as the Principal Investigator and Dr. Tribble as the Co-Investigator. The focus of this grant was on living lobar transplantation, which paralleled the development of the UVA lung transplant program. Drs. Chuck Hobson, Lorne Blackbourne, and Scott Langenburg were among the first of many UVA residents supported by various training grants related to the TCV lab. All three of these graduates of our program have been academically productive ever since their days of training in the TCV lab, as have many subsequent trainees, both those from UVA and from other institutions. The TCV lab has been continuously supported by RO1 NIH grants since that time.

In 1998, an NIH T32 Cardiovascular Surgery Research Training Grant was awarded to the lab, again with Dr. Kron as the PI and Dr. Tribble as the Co-PI. This program has been continuously funded since that time. Another RO1 grant obtained in 2000 by the TCV lab was based on the long term focus of the lab on spinal cord protection during aortic surgery. Dr. John Kern, now the Chief of the Division of TCV Surgery, was the Principal Investigator for this grant, while both Dr. Kron and Dr. Tribble were Co-Principal Investigators.  Another area of interest to the lab has been ventricular assist device development, through collaboration with researchers in the UVA School of Engineering. Some of this work was supported by the UVA Children’s Hospital with a grant to Dr. Tribble in 2001.

Victor Laubach, PhD joined the lab in ~1995 and helped provide additional focus on the basic science approaches to the work of the lab group and to the education of the residents training in the lab. In addition to Dr. Laubach, there are a number of outstanding individuals who have helped manage and run the lab over the years, including Mr. Tony Herring, who has been the manager of the lab for many years and Ashish Sharma, who obtained his PhD while working in the lab.  There have also been many productive collaborations with other current and former UVA researchers, such as Kevin Lynch from the Department of Pharmacology and Joel Linden now a Professor at the La Jolla Institute in San Diego and the founder of a company known as Adenosine Therapeutics.

Throughout the existence of the TCV lab, there has been a consistent focus on several principles. First of all, the research efforts of the lab have been related to the clinical challenges faced by the UVA TCV faculty surgeons in their clinical programs, including lung transplantation, heart failure, and aortic surgery. Second, there has been an emphasis on creating an optimal educational environment for the residents, with regular lab meetings and consistent mentoring of the medical students, basic science students, and surgical residents (both from UVA and from other programs) spending time in the lab. Third, the lab has always used some large animal models, in addition to a myriad of isolated perfused organ models and small animal models, and this focus on large animal models has allowed the surgical residents to very significantly improve their surgical skills. Fourth, there has always been an additional emphasis on publishing clinical papers related to the work of the Division. The resident trainees have consistently been very productive, publishing from 15 to 30 articles in refereed journals related to their work in the lab. Furthermore, there has been an emphasis on helping the resident trainees become outstanding surgical educators, with many of these residents being recognized by a large number of teaching awards, including numerous James Kindred Awards, given to the UVA resident considered by the graduating medical school classes to have been their single best teaching resident.

An example of an alumnus of the lab is Dr. Brett Reece, who came from his general surgery training program to spend two years in the TCV lab, funded by the T32 training grant. He was very productive during his time in the lab, publishing numerous articles. Brett went on to train in CT surgery at Colorado where he has remained on the faculty. He has established a very productive lab there, primarily studying spinal cord ischemia.

The TCV lab environment has continued to flourish and be productive up to the present time.  As evidence of this productivity, Dr. Kron has been an author or co-author of more papers published in The Annals of Thoracic Surgery than any other author in that journal’s history. The vast majority of these papers were co-authored by residents who spent time in the TCV lab. There are generally two or three UVA surgery residents working in the lab who are carrying on these traditions, with the current focus being on ‘resuscitation of marginal lungs’ for transplantation.  There will be a renewed focus on pediatric lung transplantation in the coming years. The lab group continues to welcome interest from UVA students and surgery residents, as well as from residents other training programs who can be supported with the T32 training grant.

Funding

NIH Grants:  UM1 HL008925 (Cardiothoracic Network Grant),

R01 HL119218, T32 HL007849 (Cardiothoracic Training Grant)

Selected References

Selected references illustrate the depth and breadth of the academic productivity of the faculty and residents who have been a part of this lab over the years.

Tribble CG, Kern JA, Daniel TM, Kron IL: The first single lung transplant in Virginia. Virginia Medical Quarterly 118(3): 116-167, 1991.

Ross SD, Tribble CG, Linden J, Gangemi JJ, Kron IL. Selective adenosineA2A activation reduces lung reperfusion injury following transplantation. J Heart Lung Transplant 18:994-1002, 1999.

Reece TB, Tribble CG, Maxey TS, Ellman PI, Laubach VE, Linden J, Kern JA, Kron IL. Adenosine A2A receptor agonist improves cardiac dysfunction from pulmonary ischemia-reperfusion injury. Ann Thorac Surg 79(4):1189-1195, 2005.

Gazoni LM, Tribble CG, Ellman PI, Laubach VE, Kron IL. Pulmonary macrophage inhibition, inhaled nitric oxide attenuate lung ischemia reperfusion injury. Ann Thorac Surg84:247-53, 2007.

LaPar DJ, Ailawadi G, Bhamidipati CM, Stukenborg G, Kern JA, Kron IL et al. Small prosthesis size in aortic valve replacement does not affect mortality. The Annals of Thoracic Surgery 92: 880-8, 2011.

Kron IL. Surgical Mentorship. The Journal of Thoracic and Cardiovascular Surgery 142: 489-92, 2011.

Mulloy DP, Stone ML, LaPar DJ, Sharma AK, Kron IL, et al. Ex vivo rehabilitation of non-heart-beating donor lungs in preclinical porcine model: delayed perfusion results in superior lung function. The Journal of Thoracic and Cardiovascular Surgery 144: 1208-15, 2012.

Fernandez LG, Sharma AK, LaPar DJ, Kron IL, Laubach VE. Adenosine A(1) receptor activation attenuates lung ischemia-reperfusion injury. The Journal of Thoracic and Cardiovascular Surgery 145: 1654-9, 2013.

Mulloy DP, Sharma AK, Lau CL, Kron IL, Laubach VE. Adenosine A3 receptor activation attenuates lung ischemia-reperfusion injury. Ann Thorac Surgery. 95: 1762-7, 2013

Gillen JR, Zhao Y, LaPar DJ, Stone ML, Kron IL, Lau CL. Rapamycin blocks fibrocyte migration and attenuates bronchiolitis obliterans in a murine model.  Ann Thorac Surg 95:1768-75, 2013.

Wagner CE & Kron IL. Subvalvular techniques to optimize surgical repair of ischemic mitral regurgitation.   Curr Opin Cardiol 29: 140-4, 2014.

CG Tribble & WH Merrill. The Way We Talk is the Way We Teach. Journal of Thoracic and Cardiovascular Surgery 147:1155-9, 2014.

Stone ML, LaPar DJ, Ailawadi G, Kron IL, Bergin JD, Blank RS, Kern JA. Ventricular assist devices and increased blood product utilization for cardiac transplantation.  See comment in PubMed Commons below J Card Surg 30:194-200, 2015.

LaPar DJ, Isbell JM, Mulloy DP, Stone ML, Kern JA, Ailawadi G,  Kron IL. Planned cardiac re-exploration in the intensive care unit is a safe procedure. Ann Thorac Surg 98, 1645-51, 2014.

Stone ML, LaPar DJ, Ailawadi G, Kron IL, Kern, JA. Ventricular assist devices and increased blood product utilization for cardiac transplantation. J Card Surg 30: 194-200, 2015.1

Charles EJ & Kron IL. One step closer to the elimination of primary graft dysfunction. J Thorac Cardiovasc Surg 149: 602-3, 2015.

The main focus of this program is on understanding the molecular and cellular mechanisms of lung injury relevant to lung transplantation and particularly to chronic allograft rejection. Another focus is on improving the quality of marginal lungs though a novel technique, called Ex-Vivo Lung Perfusion (EVLP).

Importance of this Research Program

Lung transplantation currently is the preferred treatment option for a variety of end-stage pulmonary diseases. Remarkable progress has occurred through refinement in technique and improved understanding of transplant immunology and microbiology. Despite these improvements donor shortages and chronic lung allograft rejection continue to plague the field and prevent it from reaching its full potential. Chronic rejection of the lung allograft is currently the major hurdle limiting long-term survival. To date prevention of known risk factors and treatment strategies have not lessened the devastating toll this process has on lung transplant survival.

What is Chronic Allograft Rejection?

Chronic allograft rejection or bronchiolitis obliterans (BO) remains the leading cause of morbidity and mortality in lung transplant recipients after the first three months, and is the primary reason why the 5- and 10-yr survival rates of lung allograft recipients are only 50% and 26%, respectively post transplantation. BO is the histological finding of chronic rejection in the lung allograft. The pathogenesis of BO although not completely understood is probably a result of multiple hits of injury and inflammation followed temporally by the development of allospecific immune responses to graft antigens. The immune response leads to further allograft injury from direct cell-to-cell cytotoxicty as well as from secretion of cytokines and chemokines. The cycle of injury, inflammation and immune activation culminate in repair, remodeling and excessive fibro-proliferation. As the lung, unlike other solid organ transplants, is constantly exposed to the external environment via the main airways, injury can occur repeatedly from allo-independent factors (for example viral infections, reflux). These events can act synergistically with allo-dependent factors (acute rejection) to compound injury. The complex interplay between injury, inflammation, repair and immunity likely explain why increasing immunosuppression alone does not effectively mitigate progression of BO.

Current Research Projects

Adenosine Signaling in Lung Transplantation Injury and Rejection

Based on the complex etiology of BO, a multi-pronged approach that affects the inflammatory and innate as well as the adaptive immune responses to injury would be most effective in mitigating BO. Ischemia-reperfusion injury is linked to the subsequent development of BO. Furthermore, early post-transplant elevation of proinflammatory mediators has been shown to be associated with alloimmunity and BO. However, unlike other solid organ transplants it is likely that frequent and repetitive subclinical injury occurs in the lung allograft since it is constantly exposed to the external environment. Thus limiting ischemia-reperfusion injury may lessen the development of BO, but likely will not alone eliminate it. The same holds true with the prevention of the other risk factors (acute rejection/viral infections/reflux). A treatment strategy that is multifaceted in prevention of inflammation and immunity is likely needed.

Adenosine and it four receptors are a critical part of the physiological negative-feedback mechanism for limitation and termination of tissue-specific and systemic inflammatory responses. Adenosine and its receptors also play roles in the adaptive immune response and in wound healing and fibrosis. One of the main projects in our laboratory is characterizing the role of adenosine, and its various receptors in chronic allograft dysfunction. We have shown the adenosine A2A receptor is important in chronic allograft injury and that agonists to this receptor can attenuate this injury (Lau and colleagues, Ann Thorac Surg. 88(4):1071-8).

Figure 1 shows allograft tracheas from mice that have been treated with adenosine A2A receptor agonists compared to no treatment controls and trachea allografts into A2A R knock-out mice. The allografts transplanted into A2A R knock-out recipients experienced the most inflammation and subsequent luminal obliteration, and adenosine A2A R agonist (ATL in figure) treated allografts showed protection from inflammation and luminal obliteration.

Cross Talk between Coagulation and Inflammation in Lung Acute Injury

It is clear the two powerful biologic systems, coagulation and inflammation, interact and contribute to the severity of the response. It is well documented that increased coagulation and impaired fibrinolysis play an important role in the pathogenesis of the various forms of acute lung injury. One active area of research in our laboratory is on the cross-talk between the coagulation and inflammatory systems in ischemia-reperfusion injury, which is a type of acute lung injury and is a significant risk factor in the future development of BO. Experiments in our laboratory have already shown that lung ischemia-reperfusion injury triggers fibrin deposition in the murine lungs and fibrin creates a proinflammatory environment. Preventing fibrin deposition with the use of plasminogen activator inhibitor-1 (PAI-1) knock-out mice (see Figure 2) reduces ischemia-reperfusion injury and inflammation (see Figure 3). This finding may lead to novel treatment strategies for ischemia-reperfusion (JTCVS, 137(5):1241-1248, 2009).

Stem Cells and Bronchiolitis Obliterans (BO) Development

Loss of epithelial cells is one of the key factors that lead to airway fibrosis.  Loss of epithelial cells may decrease the barrier to host cell infiltration into the lumen, allowing deposition of extracellular matrix, with subsequent obliteration of the airway. We are trying to determine whether injection of epithelial cells/progenitor cells from the recipient into the lumen of the donor trachea could prevent bronchiolitis obliterans (BO) in a mouse heterotopic tracheal transplantation (HTT) model.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) have shown therapeutic potential in acute lung injury. Recently, placental-derived human mesenchymal stem cells (PMSCs) have exhibited similarities with BM-MSCs in terms of regenerative capabilities and immunogenicity. We are testing whether treatment with PMSCs would reduce the development of bronchiolitis obliterans BO in a murine heterotopic tracheal transplant model.

mTOR Inhibition Prevent BO Development

We have found that fibrocytes, a circulating population of mesenchymal progenitor cells, are present in higher numbers in the circulation of patients destined to develop BO and that these cells contribute to the histologic lesions of BO suggesting their role as potential biomarkers for this process.  We also found that migration of fibrocytes into lung allografts and contribution of the fibrocytes to BO depends on the mammalian target of rapamycin (mTOR).  We are testing the mechanisms of mTOR inhibition (rapamycin) can prevent development of BO through: (1) affecting fibrocytes recruitment; (2) promoting epithelial progenitor cells and (3) altering regulatory B cells.

Increasing the Usage of Marginal Lung via Ex-vivo Lung Perfusion with a selective adenosine 2A receptor agonist, Regadenoson

Ischemia-reperfusion injury (IRI) remains the leading cause of early morbidity and mortality after lung transplantation and also predisposes to bronchiolitis obliterans, the major limitation to long-term survival after transplant. IRI is known clinically as (PGD) which entails diffuse alveolar damage and hypoxemia in the acute post-lung transplant period. Currently there are no preventative therapies for PGD.  Furthermore because of the concern for PGD, surgeons are reluctant to use marginal donor lungs. In multi-organ donors the lungs are the least likely solid organ to be deemed transplantable.

The pathogenesis of IRI has historically been characterized by the recruitment and extravasation of neutrophils. However we have recently reported that one subset of CD4+ T cells, Type I invariant natural killer T (iNKT) cells, are key initiators of IRI via IL-17 production which drives the infiltration of neutrophils – the end effector cells for tissue injury. Selective agonists of the adenosine 2A receptor (A2AR), an anti-inflammatory G protein-coupled receptor, have been shown to inhibit the activity of most inflammatory cells (including neutrophils and iNKT cells). Our laboratory has extensive preclinical evidence demonstrating that 1) A2AR agonists potently prevent IRI after lung transplantation and 2) that use of A2AR agonist combined with ex-vivo lung perfusion (EVLP) enhances EVLP-mediated donor lung rehabilitation and successful transplantation. Preliminary data shows that A2AR agonist attenuates IRI largely by blocking the activation of iNKT cells.

Regadenoson (Lexiscan®) is a selective A2AR agonist drug that targets A2AR-bearing cells and is FDA approved as a pharmacologic stress agent indicated for radionuclide myocardial perfusion imaging. A recently completed NIH funded study successfully used a 12-hour regadenoson infusion safely and efficaciously in sickle cell adults with acute chest syndrome. The current proposal requests support fo*** r both: 1) a human phase I pilot trial evaluating the safety of regadenoson for the prevention of IRI after lung transplantation and 2) use of regadenoson in human EVLP as a novel strategy to recondition marginal donor lungs and limit the IRI seen in these lungs when transplanted. Regadenoson is an innovative therapy with great promise to attenuate IRI and thus improve both short- and long-term clinical outcomes.

Many lung transplant programs have increased their volume of lung transplants performed by accepting marginal donor criteria, but even with the use of these donors the need greatly outweighs the number of available lung donors.  Recently, a novel, recent FDA-approved EVLP technique (Figure 4) has been developed that allows previously unusable (marginal) donor lungs to be rehabilitated, tested, and successfully used in recipients. EVLP has been shown to reduce the degree of IRI in marginal lungs and has the potential to vastly increase the donor lung supply. We are trying to combine the novel EVLP technique with the selective A2AR agonist, Regadenoson to improve quality of the marginal lungs.  This could help further expand the donor pool and lessen PGD. Our long term goal is to improve the human marginal lungs quality and apply our experimental findings to clinical operation.

This work is funded by a relatively new RO1 NIH grant with Dr. Lau as the Principle Investigator.  The NIH grant number is: R01 HL128492

Contact

For more information about the Lung Transplantation Research Program at the University of Virginia, please contact Dr. Lau:

Victor Laubach, PhD
Mark Roeser, MD
University of Virginia
Thoracic Surgery
PO Box 800679
Charlottesville, VA 22908

Telephone: 434-924-8016

ormerly managed by Dr. Benjamin Kowzower, MD

The Health Services and Outcomes Research in Thoracic Surgery program is dedicated to improving the quality of care for thoracic surgery patients. The program is led by Benjamin D. Kozower, MD, MPH who is a general thoracic surgeon and completed his Master of Public Health degree at the University of Virginia. Health services research examines health care quality and effectiveness, patient outcomes, access to care, health care costs and financing, new technologies, and other critical topics. We focus on some of the most complex and challenging issues currently affecting health care in the United States. Findings from health services research inform the health care policymaking process, lead to improvements in clinical practice, and help shape the manner in which health care will be delivered and paid for in the future.

Current Research Projects

We are currently working on several interesting projects funded by the Patient Centered Outcomes Research Institute which include:

Comparison of patient-centered outcomes for lung cancer resection patients followed with alternative intervals of surveillance imaging.

The National Cancer Data Base (NCDB) provides real world national lung cancer resection and surveillance data on over 70% of lung cancers. We will compare the effectiveness of the three most common surveillance intensities (computed tomography scans every 3 months vs. 6 months vs. annually) on stakeholder selected outcomes of survival, recurrence, and identification of new lung cancers. Analyses will be risk adjusted for differences in patient characteristics, including tumor characteristics, patient age, comorbid disease, and for the competing risk of death.

Implementation of post-treatment surveillance of patient-reported outcomes with integrated display in electronic medical records.

A patient-centered approach to lung cancer surveillance needs to incorporate patient reported outcomes. Patients seen at the University of Virginia Cancer Center will be invited to participate in an assessment of their reported outcomes over multiple domains available in the Patient Reported Outcomes Measurement Information System (PROMIS®) These data will be integrated into electronic health records to improve patient care by triggering telephone calls, expedited office visits, or referrals to appropriate ancillary support. This information will also provide a robust platform to design a patient-centered surveillance strategy following resection.

Determination of the clinical importance of surgical outcome definitions and their ability to differentiate hospital performance.

A variety of surgical outcome definitions and follow-up periods are used as quality metrics by different quality agencies. Importantly, it remains unclear if commonly reported outcomes actually differentiate between good and poor performing hospitals and surgeons. We will use longitudinal data from SEER-Medicare (Surveillance, Epidemiology and End Results) to study lung and esophageal cancer resection outcomes. We will evaluate a variety of outcomes including different mortality definitions, hospital readmission definitions and discharge status to determine if there are meaningful clinical differences between them and their impact on differentiating hospital performance. We published our first project with SEER-Medicare lung cancer resection patients in 2014. This work demonstrated that 90-day mortality (8.5%) is almost double that of 30-day mortality (4.8%). This is important because the 30-day mortality metric reported by Medicare does not adequately represent a patient’s true mortality risk following surgery. We have published two other manuscripts related to this work in 2014 and 2015 and have submitted a fourth manuscript examining readmission after esophagectomy for cancer.

Determination of patient satisfaction and recurrence rates following hiatal hernia repair.

The general thoracic surgery service at the University of Virginia has dramatically increased its volume of benign esophageal surgery over the past five years. We have initiated a prospective study to evaluate our short and long-term outcomes following hiatal hernia repair out to 5-years. The prospective cohort is evaluated at 30 days and yearly with radiographic imaging for recurrence and validated symptom specific quality of life measurements. This is an important study because the popularity of laparoscopic hiatal hernia surgery has increased dramatically despite relatively poor published long-term results. As of June 30, 2015, we have enrolled 310 patients to the study. This is a highly productive and critical study and a logical integration of our clinical and research missions.

Recent Research Publications

1. McMurry TL, Hu Y, Blackstone EH, Kozower BD. Propensity scores: Methods, considerations and applications in the Journal of Thoracic and Cardiovascular Surgery. J Thorac Cardiovasc Surg. 2015;150(1):14-9.
2. Hu Y, McMurry T, Isbell JM, Stukenborg GJ, Kozower BD. Readmission after lung cancer resection is associated with a six-fold increase in 90-day postoperative mortality. J Thorac Cardiovasc Surg. 2014; 148(5):2261-67.
3. Hu Y, Craig SJ, Rowlingson JC, Morton SP, Thomas CJ, Persinger MB, Isbell J, Lau CL, *Kozower BD. Early removal of urinary catheter after surgery requiring thoracic epidural: a prospective trial. J Card & Vasc Anesth. 2014;28(5):1302-6.
4. Walters DM, McMurry T, Isbell JM, Stukenborg GJ, Kozower BD. Understanding mortality as a quality indicator following esophagectomy. Ann Thorac Surg. 2014; In Press.\
5. Hu Y, McMurry T, Isbell JM, Stukenborg GJ, Kozower BD. Postoperative mortality is an inadequate quality indicator for lung cancer resection. Ann Thorac Surg. 2014; 97(3):973-9.
6. Hu Y, Ezekian B, Wells KM, Burks SG, Jones DR, Lau CL, Schirmer BD, Kozower BD. Long term satisfaction and medication dependence after antireflux surgery. Ann Thorac Surg. 2013; 96(4):1246-51.
7. LaPar DJ, Stukenborg GJ, Lau CL, Jones DR, Kozower BD. Differences in reported esophageal cancer resection outcomes between national clinical and administrative databases. J Thorac Cardiovasc Surg. 2012; 144(5):1152-59.
8. LaPar DJ, Kron IL, Jones DR, Stukenborg GJ, Kozower BD. Hospital procedure volume should not be used as a measure of surgical quality. Ann Surg. 2012; 256(4):606-15.
9. Kozower BD and Stukenborg GJ. The relationship between hospital lung cancer resection volume and patient mortality risk. Ann Surg. 2011; 254(6):1032-7.

Funding

• Agency for Healthcare Research and Quality: K08 – HS18049. Mortality assessment in lung cancer resection. Benjamin D. Kozower, MD, Principle Investigator. Funding period: 07/01/10-06/30/15.
• Patient Centered Outcomes Research Institute: R-APD-1306-00727. Improving the effectiveness of routine surveillance following lung cancer resection. Benjamin D. Kozower, MD, Principle Investigator. Funding period: 07/01/14-6/30/17.

Contact  

For more information about the Health Services and Outcomes Research in Thoracic Surgery program at the University of Virginia, please contact Dr. Kozower:

Benjamin D. Kozower, MD, MPH
University of Virginia, Thoracic Surgery
PO Box 800679
Charlottesville, VA 22908
Telephone: 434.924.2145
Email: bdk8g@virginia.edu

Dr. Roeser has organized a project which proposes to study the role of rapamycin in treatment of bronchiolitis obliterans syndrome (BOS) in pediatric lung transplantation using a small animal model. The proposed small animal model of BOS will emulate one that was developed at the University of Iowa and will take advantage of the considerable experience of The TCV Lab in transplantation in immature animals. The intent is to use CT scans to track the development of BOS, which is the approach used clinically to follow pediatric lung transplant patients. Briefly, a left lower lobe transplant will be performed in an immature animal. After these transplants CT scans will be used to measure BOS and track fibrocyte levels and to evaluate the effectiveness of rapamycin in ameliorating BOS. The hypothesis to be studied is that the rapamycin will decrease the fibrocyte levels and attenuate BOS in these animals.