Effects of Sirolimus on Lung function in patients with Lymphangioleiomyomatosis

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a progressive lungs disease that affects women at reproductive years. Sirolimus inhibits mammalian target of rapamycin (mTOR) and its administration in past studies was hopeful in treatment of patients with LAM. The aim of this study was to evaluate sirolimus therapy on lung function in LAM patients. METHODS: We conducted a trial to evaluate the effect of sirolimus on six patients with LAM who had severe or very severe obstructive lung disease, and one-year follow up. Maintenance level of Sirolimus was 10-15 ng/ml. Serial visits (including physical examination, evaluation of signs and symptoms of disease and adverse events due to treatment), spirometry, 6MWT done at baseline 3, 6, 9 and 12 months after. Spirometric parameters walk distance and O(2) saturationbefore and after exercise at first and the end of treatment were measured. RESULTS: Four patients had TSC-LAM while the other 2 patients had S-LAM. The mean level of sirolimus was 13 ng/ml after one-year treatment. Mean FEV1 at enrollment and end of study was 1000cc (33% predict) and 1228cc (42% predict) respectively (P=0.674). The mean FVC at baseline and end of study was 1648cc (49% predict) and 1866cc (55% predict) (P=0.996). The mean FEV1/FVC at enrollment and the end of treatment was 58% and 62% respectively (P=0.753). The mean FEF25-75 at first and at the end of treatment was 16% and 26%, respectively (P=0.028). The mean walk distance in 6MWT at first and at the end of study was 315 meters (P=0.9). The mean percentage of O(2) saturation at rest was 84% and 92% at first and at the end of study (P=0.104). CONCLUSION: In LAM patients, sirolimus has been shown stabilizeto or improve lung function, rest and exertional O(2) saturation. Sirolimus was effective in LAM patients who had severe or very severe physiological disorders.