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The NHLBI Lymphangioleiomyomatosis (LAM) Registry: Longitudinal Analysis to Determine the Natural History of LAM

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2017, MS, University of Cincinnati, Medicine: Clinical and Translational Research.
Introduction: Lymphangioleiomyomatosis (LAM) is a rare, female-predominant, low-grade metastasizing neoplasm characterized by proliferation of abnormal smooth muscle cells and progressive destruction of lung parenchyma. Improved understanding of the natural history of LAM and identification of prognostic biomarkers can help guide management decisions in this patient population. Methods: Over a three-year period (1998–2001), 246 patients with LAM were enrolled into a National Heart, Lung, and Blood Institute (NHLBI) funded registry at six sites across the United States. Longitudinal data was collected at every 6-12 month intervals until 2003. The data collected included quality of life questionnaires, computed tomography (CT) scan findings, pulmonary function test (PFT) measurements, and serum specimens. These data and samples were subsequently de-identified and stored at the National Disease Research Interchange (NDRI) - an agency that contracts with the NHLBI to store and distribute samples. We obtained the de-identified data and serum specimens collected as part of this registry from the NDRI. In addition, we queried the National Death Index and the United Network for Organ Sharing databases to determine the patients who had either deceased or undergone lung transplantation after enrolling in this registry. A linear mixed effects model was employed to compute the rate of lung function decline and to correlate it with various clinical characteristics and biomarkers such as serum vascular endothelial growth factor-D (VEGF-D). Prognostic variables associated with progression to death/lung transplantation were identified using a Cox proportional hazard model. Results: After excluding patients with unclear diagnosis (n=17) and the patients who had undergone lung transplantation prior to study enrollment (n=12), we analyzed the data from the remaining 217 patients. The average rate of decline of forced expiratory volume in 1-second (FEV1) and forced vital capacity (FVC) was 89±17 mls/year and 71±57 mls/year, respectively. Rate of decline of FEV1 was significantly negatively impacted by the baseline FEV1 (p<0.0001), FVC (p=0.007), and CT score (p=0.02). Pre-menopausal women declined faster than post-menopausal women (118mls/year versus 74mls/year, p=0.003). Other variables such as serum VEGF-D, spontaneous pneumothorax, and tuberous sclerosis complex (TSC) versus sporadic-LAM did not affect the rate of decline of FEV1. From our cohort of 217 patients, 26 patients had died, and 43 patients had received lung transplant prior to the data censor date of 12/31/2014. The 5-, 10-, 15-, and 20-year survival rates were estimated to be 95%, 85%, 75%, and 64%, respectively. Baseline PFTs, the trajectory of PFTs, serum VEGF-D, CT score, and bronchodilator responsiveness on spirometry can predict progression to death/transplant, with baseline PFTs and postmenopausal status being the biggest determinants of future progression to death/transplant. Conclusions: LAM is a progressive disease and, in general, lung function declines at a rate that is 3-4 times faster than historical, age-matched, healthy controls. Baseline physiological and radiological disease severity, as well as menopausal status, has a significant impact on the rate of lung function decline. The median survival in women with LAM is greater than 20 years, and is significantly affected by the baseline PFTs and menopausal status.
Erin Nicole Haynes, Dr.P.H. (Committee Chair)
Hye-Seung Lee, M.S.Ph.D.M.P.H. (Committee Member)
Francis McCormack, M.D. (Committee Member)
47 p.

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Citations

  • Gupta, N. (2017). The NHLBI Lymphangioleiomyomatosis (LAM) Registry: Longitudinal Analysis to Determine the Natural History of LAM [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1504879473662385

    APA Style (7th edition)

  • Gupta, Nishant. The NHLBI Lymphangioleiomyomatosis (LAM) Registry: Longitudinal Analysis to Determine the Natural History of LAM. 2017. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1504879473662385.

    MLA Style (8th edition)

  • Gupta, Nishant. "The NHLBI Lymphangioleiomyomatosis (LAM) Registry: Longitudinal Analysis to Determine the Natural History of LAM." Master's thesis, University of Cincinnati, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1504879473662385

    Chicago Manual of Style (17th edition)