The purpose of this study was to determine the clinical presentation and severity of TSC in adult women. Seventy-nine women, age eighteen or older were enrolled between 1995 and 2009. Patients were evaluated using history, physical examination, pulmonary function testing, chest X-ray, abdominal computed tomography, high-resolution chest computed tomography and brain magnetic resonance imaging. Forty-five of the patients received a TSC diagnosis in adulthood. Thirty of these met clinical criteria for TSC in childhood but remained undiagnosed for a median of 22 years, and fifteen were greater than 18 years old before manifesting sufficient disease characteristics to make the diagnosis. Compared to those diagnosed in childhood, individuals with adult penetrance had fewer major TSC features, fewer skin lesions, were less likely to have seizures, and were more likely to present with pulmonary lymphangioleiomyomatosis or angiomyolipomas. No males were included and patients were biased towards those having pulmonary lymphangioleiomyomatosis. In this study, women who received a TSC diagnosis in adulthood either manifested TSC symptoms later in life or experienced a significant delay to diagnosis, but were still at risk for developing life-threatening pulmonary and renal TSC manifestations. Failure to recognize TSC when manifestations first appear contributes to increased morbidity and mortality because screening and interventions are delayed and early diagnosis can offer individuals and their families an opportunity to make informed childbearing decisions.
The aim of our study was to evaluate the effect of sirolimus in LAM patients with rapidly progressive or severe lung disease and those with chylous effusions and lymphangioleiomyomas, a population in whom sirolimus has not been tested. Because most patients were participating in a natural history study at National Institutes of Health, we had physiologic and radiologic data preceding sirolimus therapy for several years for most patients and, therefore, were able to compare pre- and post-therapy data. Lung function, chylous effusions, and lymphangioleiomyomas before and during sirolimus therapy were measured. During a mean of 2.5 years before sirolimus therapy, forced expiratory volume in the first second (FEV1) and lung diffusion capacity (DLCO) declined, respectively, 2.80.8 and 4.80.9 % predicted per year. In contrast, during a mean of 2.6 years of sirolimus therapy, FEV1 and DLCO, increased, respectively, 1.80.5 and 0.80.5 % predicted per year (p<0.001). Twelve patients with chylous effusions and 11 with lymphangioleiomyomas experienced almost complete resolution of these abnormalities. In two of the 12 patients, sirolimus therapy enabled discontinuation of pleural fluid drainage. Sirolimus therapy is associated with improvement or stabilization of lung function and reduction of the size of chylous effusions and lymphangioleiomyomas in patients with lymphangioleiomyomatosis.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
National Heart, Lung, and Blood Institute
Zip Code
Oyerinde, Oyetewa; Buccine, Danielle; Treichel, Alison et al. (2018) Fibrous cephalic plaques in tuberous sclerosis complex. J Am Acad Dermatol 78:717-724
Pacheco, Gustavo G; Jones, Amanda M; Yao, Jianhua et al. (2018) Mounier-Kuhn Syndrome Mimicking Lymphangioleiomyomatosis. Chest 153:e19-e23
Sapp, Julie C; Johnston, Jennifer J; Driscoll, Kate et al. (2018) Evaluation of Recipients of Positive and Negative Secondary Findings Evaluations in a Hybrid CLIA-Research Sequencing Pilot. Am J Hum Genet 103:358-366
Lamattina, Anthony M; Taveira-Dasilva, Angelo; Goldberg, Hilary J et al. (2018) Circulating biomarkers from the phase I trial of sirolimus and autophagy inhibition for patients with lymphangioleiomyomatosis (SAIL). Chest :
Gopalakrishnan, Vissagan; Jones, Amanda M; Julien-Williams, Patricia et al. (2018) Pseudoneutropenia in lymphangioleiomyomatosis (LAM) patients receiving sirolimus: evaluation in a 100 patient cohort. ERJ Open Res 4:
Steagall, Wendy K; Pacheco-Rodriguez, Gustavo; Darling, Thomas N et al. (2018) The Lymphangioleiomyomatosis Lung Cell and Its Human Cell Models. Am J Respir Cell Mol Biol 58:678-683
Avila, Nilo A; Dwyer, A J; Moss, J (2018) Reply to ""Renal Lesions in Lymphangioleiomyomatosis and Tuberous Sclerosis Complex Are Rarely Biologically Aggressive"". AJR Am J Roentgenol 210:W132
Gupta, Nishant; Lee, Hye-Seung; Ryu, Jay H et al. (2018) The NHLBI LAM Registry: Prognostic Physiologic and Radiologic Biomarkers Emerge From a 15-Year Prospective Longitudinal Analysis. Chest :
Le, Kang; Steagall, Wendy K; Stylianou, Mario et al. (2018) Effect of beta-agonists on LAM progression and treatment. Proc Natl Acad Sci U S A 115:E944-E953
Larsen, Thomas C; Gopalakrishnan, Vissagan; Yao, Jianhua et al. (2018) Optimization of a secondary VOI protocol for lung imaging in a clinical CT scanner. J Appl Clin Med Phys 19:271-280

Showing the most recent 10 out of 97 publications