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
16
Fiscal Year
2011
Total Cost
$3,094,983
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
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