• Angelo M Taveira-DaSilva, Olanda Hathaway, Mario Stylianou, and Joel Moss.
• Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1590, USA. dasilvaa@nhlbi.nih.gov
• Ann. Intern. Med. 2011 Jun 21;154(12):797-805, W-292-3.

BackgroundLymphangioleiomyomatosis (LAM) is a disorder that affects women and is characterized by cystic lung destruction, chylous effusions, lymphangioleiomyomas, and angiomyolipomas. It is caused by proliferation of abnormal smooth muscle-like cells. Sirolimus is a mammalian target of rapamycin inhibitor that has been reported to decrease the size of neoplastic growths in animal models of tuberous sclerosis complex and to reduce the size of angiomyolipomas and stabilize lung function in humans.ObjectiveTo assess whether sirolimus therapy is associated with improvement in lung function and a decrease in the size of chylous effusions and lymphangioleiomyomas in patients with LAM.DesignObservational study.SettingThe National Institutes of Health Clinical Center.Patients19 patients with rapidly progressing LAM or chylous effusions.InterventionTreatment with sirolimus.MeasurementsLung function and the size of chylous effusions and lymphangioleiomyomas before and during sirolimus therapy.ResultsOver a mean of 2.5 years before beginning sirolimus therapy, the mean (±SE) FEV1 decreased by 2.8%±0.8% predicted and diffusing capacity of the lung for carbon monoxide (Dlco) decreased by 4.8%±0.9% predicted per year. In contrast, over a mean of 2.6 years of sirolimus therapy, the mean (±SE) FEV1 increased by 1.8%±0.5% predicted and Dlco increased by 0.8%±0.5% predicted per year (P<0.001). After beginning sirolimus therapy, 12 patients with chylous effusions and 11 patients with lymphangioleiomyomas experienced almost complete resolution of these conditions. In 2 of the 12 patients, sirolimus therapy enabled discontinuation of pleural fluid drainage.LimitationsThis was an observational study. The resolution of effusions may have affected improvements in lung function.ConclusionSirolimus therapy is associated with improvement or stabilization of lung function and reduction in the size of chylous effusions and lymphangioleiomyomas in patients with LAM.Primary Funding SourceIntramural Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health.

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