Candidate?s Plans/Training: The candidate plans a career as an independent clinical investigator focusing on patient oriented research related to advanced lung disease and lung transplantation. Training will include formal epidemiological course work in patient oriented research, a mentored laboratory experience, and closely mentored completion of the research protocol. Environment: The University of Pennsylvania is a uniquely suited environment for this training award. The Center for Clinical Epidemiology and Biostatistics will provide formal didactic training. The Metabolic Magnetic Resonance Research and Computing Center will provide a mentored laboratory experience. Research: Obliterative Bronchiolitis (OB) is recognized as a form of chronic allograft rejection and affects as many as 60 to 80% of lung transplant recipients between 5 and 10 years after transplantation. Diagnosis of OB is difficult to make, yet detection of the disease is important because patients who have OB detected early may have improved survival. Current techniques in detection include lung biopsy, which is insensitive and morbid, and spirometry, which detects disease after it has progressed. Recently, non-invasive functional MRI methods using hyperpolarized, non-radioactive 3He gas and magnetic labeling of blood, termed """"""""Arterial Spin-Tagging"""""""" (AST) have been developed which detect ventilation and perfusion (V & Q) disturbances in patients with airway obstruction, such as in OB. The overall hypothesis of the proposal is that a predictive model combining clinical risk factors for OB with the detection of airspace and perfusion disturbances using 3He and AST MR imaging will identify OB earlier than conventional techniques. The study has three specific aims: (1) a retrospective cohort study to examine the relationship between clinical parameters and the incidence of OB; (2) a prospective cohort study to test the hypothesis that V & Q imaging using hyperpolarized 3He and AST MRI can differentiate between normal subjects and patients with varying degrees of airway obstruction and (3) a prospective cohort study to test the hypothesis that V & Q as visualized by 3He and AST MRI following lung transplant predicts patients who will develop OB.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZHL1-CSR-F (M1))
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Colombini-Hatch, Sandra
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University of Pennsylvania
Internal Medicine/Medicine
Schools of Medicine
United States
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Lipson, David A (2006) Tiotropium bromide. Int J Chron Obstruct Pulmon Dis 1:107-14
Lipson, David A (2004) Redefining treatment in COPD: new directions in bronchodilator therapy. Treat Respir Med 3:89-95
Kreider, Mary Elizabeth; Lipson, David A (2003) Bronchoscopy for atelectasis in the ICU: a case report and review of the literature. Chest 124:344-50
Lipson, David A; Roberts, David A; Hansen-Flaschen, John et al. (2002) Pulmonary ventilation and perfusion scanning using hyperpolarized helium-3 MRI and arterial spin tagging in healthy normal subjects and in pulmonary embolism and orthotopic lung transplant patients. Magn Reson Med 47:1073-6