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Gender, Sex Hormones and Respiratory Disease pp 173–187Cite as

Lymphangioleiomyomatosis

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Part of the book series: Respiratory Medicine ((RM))

Abstract

Lymphangioleiomyomatosis (LAM) is a rare progressive cystic lung disease that affects women almost exclusively, occurring in a sporadic form and in association with Tuberous Sclerosis Complex. remendous progress has been made in understanding the pathogenesis of this disorder, leading to advances in noninvasive diagnostic approaches, and a targeted therapy has now been FDA-approved for treatment of LAM (rapamycin). In LAM, progressive decline in lung function occurs as dysregulated smooth muscle-like cells (LAM cells) of uncertain origin infiltrate the lung, disrupting lymphatics and leading to parenchymal destruction and cyst formation. LAM cells have constitutive activation of the mechanistic target of rapamycin (mTOR) due to sporadic or germline mutations in tuberous sclerosis genes (TSC1 or TSC2). Inhibition of mTOR by rapamycin suppresses disease progression as was demonstrated in the Multicenter International Lymphangioleimyomatosis Efficacy of Sirolimus (MILES) trial. In animal models of LAM and in vitro cellular studies, estrogen increases cell proliferation and migration. The reason for the marked gender discrepancy remains unknown, and at this time, hormone-modulating therapies remain largely unproven or insufficiently studied in patients with LAM.

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Authors and Affiliations

  1. Division of Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, 1611 21st Avenue South, T-1218 Medical Center North, Nashville, TN, 37232, USA

    Jeannette Zinggeler Berg MD, PhD

  2. Division of Pulmonary Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, 2200 Children’s Way, Nashville, TN, 37232-9500, USA

    Lisa Young MD

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  1. Vanderbilt University Medical Center, Nashville, Tennessee, USA

    Anna R. Hemnes

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Berg, J.Z., Young, L. (2016). Lymphangioleiomyomatosis. In: Hemnes, A. (eds) Gender, Sex Hormones and Respiratory Disease. Respiratory Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-23998-9_8

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