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Original Research |

Changes in Lung Function and Chylous Effusions in Patients With Lymphangioleiomyomatosis Treated With Sirolimus

Angelo M. Taveira-DaSilva, MD, PhD; Olanda Hathaway, CRNP; Mario Stylianou, PhD; and Joel Moss, MD, PhD
[+] Article and Author Information

From the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.


Acknowledgment: The authors thank Drs. Martha Vaughan, Wendy Steagall, and Gustavo Pacheco-Rodriguez for critical review of the manuscript.

Grant Support: By the Intramural Research Program, NHLBI, NIH (protocol 95-H-0186).

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M10-1139.

Reproducible Research Statement:Study protocol: Available from the Cardiovascular and Pulmonary Branch, NHLBI. Data set: Available from the Cardiovascular and Pulmonary Branch, NHLBI, after approval by the NHLBI, institutional review board, and the institutional review board of the requesting investigator and completion of a Material Transfer Agreement. Statistical code: Not available.

Requests for Single Reprints: Angelo M. Taveira-DaSilva, MD, PhD, Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 6D05, MSC 1590, Bethesda, MD 20892-1590; e-mail, dasilvaa@nhlbi.nih.gov.

Current Author Addresses: Drs. Taveira-DaSilva and Moss and Ms. Hathaway: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 6D05, MSC 1590, Bethesda, MD 20892-1590.

Dr. Stylianou: Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockledge 2/Room 9198, MSC 7938, Bethesda, MD 20892-7938.

Author Contributions: Conception and design: A.M. Taveira-DaSilva, M. Stylianou, J. Moss.

Analysis and interpretation of the data: A.M. Taveira-DaSilva, M. Stylianou, J. Moss.

Drafting of the article: A.M. Taveira-DaSilva, M. Stylianou, J. Moss.

Critical revision for important intellectual content: M. Stylianou, J. Moss.

Final approval of the article: M. Stylianou, J. Moss.

Provision of study materials or patients: J. Moss.

Statistical expertise: M. Stylianou.

Collection and assembly of data: A.M. Taveira-DaSilva, O. Hathaway, J. Moss.


Ann Intern Med. 2011;154(12):797-805. doi:10.7326/0003-4819-154-12-201106210-00007
Text Size: A A A

Background: Lymphangioleiomyomatosis (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.

Objective: To 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.

Design: Observational study.

Setting: The National Institutes of Health Clinical Center.

Patients: 19 patients with rapidly progressing LAM or chylous effusions.

Intervention: Treatment with sirolimus.

Measurements: Lung function and the size of chylous effusions and lymphangioleiomyomas before and during sirolimus therapy.

Results: Over 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.

Limitations: This was an observational study. The resolution of effusions may have affected improvements in lung function.

Conclusion: Sirolimus 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 Source: Intramural Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health.

Figures

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Figure 1.
FEV1 (top) and Dlco (bottom) measurements obtained at each visit before and after sirolimus therapy.

Data at 0 y were obtained just before starting sirolimus therapy. One of the 19 patients with chylothorax and continuous pleural drainage could not undergo pulmonary function tests. Dlco = diffusing capacity of the lung for carbon monoxide.

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Figure 2.
Mean annual changes in FVC, FEV1, and Dlco before and after sirolimus therapy in patients with lymphangioleiomyomatosis.

Data were obtained by using mixed-effects models. During sirolimus therapy, the FVC, FEV1, and Dlco increased instead of decreasing. Dlco = diffusing capacity of the lung for carbon monoxide.

* Eighteen patients were included in these analyses because 1 patient could not undergo pulmonary function tests.

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Figure 3.
CT scans in 3 patients with lymphangioleiomyomatosis before and after sirolimus therapy.

CT = computed tomography. A. CT scan of a 29-year-old woman with bilateral chylothorax (black arrows). B. Repeated CT scan of the same patient 30 months after starting sirolimus therapy that shows complete resolution of the pleural effusions. C. CT scan of a 45-year-old woman with bilateral lung infiltrates. D. Repeated CT scan of the same patient performed after 2.5 years of sirolimus therapy that shows complete clearing of the infiltrates; her lung function also had improved. E. CT scan of a 39-year-old woman with a large lymphangioleiomyoma (white arrow). F. Repeated CT scan of the same patient after 11 months of sirolimus therapy that shows the lymphangioleiomyoma completely resolved.

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Appendix Figure.
CT scan in a patient with lymphangi-oleiomyomatosis with pleural effusion requiring persistent drainage.

CT = computed tomography. A. CT scan of a 62-year-old woman who had undergone unsuccessful chemical pleurodesis and required daily drainage of substantial amounts of pleural fluid. B. Repeated CT scan after 6 months of sirolimus therapy showing nearly complete resolution of pleural effusion.

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Summary for Patients

Sirolimus Therapy in Patients With Lymphangioleiomyomatosis

The full report is titled “Changes in Lung Function and Chylous Effusions in Patients With Lymphangioleiomyomatosis Treated With Sirolimus.” It is in the 21 June 2011 issue of Annals of Internal Medicine (volume 154, pages 797-805). The authors are A.M. Taveira-DaSilva, O. Hathaway, M. Stylianou, and J. Moss.

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