Sustained Effects of Sirolimus on Lung Function and Cystic Lung Lesions in Lymphangioleiomyomatosis.
[lymphangioleiomyomatosis]
Rationale. Sirolimus therapy stabilizes lung function and reduces the size of chylous effusions and lymphangioleiomyomas in patients with lymphangioleiomyomatosis. Objectives. To determine whether sirolimus has beneficial effects on lung function, cystic areas and adjacent lung parenchyma, whether these effects are sustained, and sirolimus is well tolerated by patients. Methods. Lung function decline over time, lung volume occupied by cysts (cyst score), and lung tissue texture in the vicinity of the cysts, were quantified with a computer-aided diagnosis system, in 38 patients. Then we compared cyst scores from the last study off sirolimus with studies done on sirolimus therapy. In 12 patients, we evaluated rates of change in lung function and cyst scores off and on sirolimus. Measurements and results. Sirolimus reduced yearly declines in FEV1 (-2.3±0.1 versus 1.0±0.3 % predicted, p<0.001) and DLCO (-2.6±0.1 versus 0.9±0.2 % predicted, p<0.001). Cyst scores 1.2±0.8 years (30.5±11.9 %), and 2.5±2 years (29.7±12.1 %) after initiating sirolimus were not significantly different from pre-treatment values (28.4±12.5 %). In 12 patients, followed for five years, a significant reduction in rates of yearly decline in FEV1 (-1.4±0.2 versus 0.3±0.4 % predicted, p=0.025) was observed. Analyses of 104 computed tomography scans showed a non-significant (p=0.23) reduction in yearly rates of change of cyst scores (1.8±0.2 versus 0.3±0.3 %, p=0.23), and lung texture features. Despite adverse events, most patients were able to continue sirolimus therapy. Conclusions. Sirolimus therapy slowed down lung function decline and increase in cystic lesions. Most patients were able to tolerate sirolimus therapy.
