Yao Jianhua, Taveira-DaSilva Angelo M, Jones Amanda M, Julien-Williams Patricia, Stylianou Mario, Moss Joel
1 Radiology and Imaging Sciences Department.
Am J Respir Crit Care Med. 2014 Dec 1;190(11):1273-82. doi: 10.1164/rccm.201405-0918OC.
Sirolimus therapy stabilizes lung function and reduces the size of chylous effusions and lymphangioleiomyomas in patients with lymphangioleiomyomatosis.
To determine whether sirolimus has beneficial effects on lung function, cystic areas, and adjacent lung parenchyma; whether these effects are sustained; and whether sirolimus is well tolerated by patients.
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 on 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.
Sirolimus reduced yearly declines in FEV1 (-2.3 ± 0.1 vs. 1.0 ± 0.3% predicted; P < 0.001) and diffusing capacity of carbon monoxide (-2.6 ± 0.1 vs. 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 pretreatment values (28.4 ± 12.5%). In 12 patients followed for 5 years, a significant reduction in rates of yearly decline in FEV1 (-1.4 ± 0.2 vs. 0.3 ± 0.4% predicted; P = 0.025) was observed. Analyses of 104 computed tomography scans showed a nonsignificant (P = 0.23) reduction in yearly rates of change of cyst scores (1.8 ± 0.2 vs. 0.3 ± 0.3%; P = 0.23) and lung texture features. Despite adverse events, most patients were able to continue sirolimus therapy.
Sirolimus therapy slowed down lung function decline and increase in cystic lesions. Most patients were able to tolerate sirolimus therapy.
西罗莫司治疗可稳定淋巴管平滑肌瘤病患者的肺功能，减小乳糜性胸腔积液和淋巴管平滑肌瘤的大小。
确定西罗莫司对肺功能、囊性区域及相邻肺实质是否有有益作用；这些作用是否持续；以及患者对西罗莫司的耐受性是否良好。
使用计算机辅助诊断系统对38例患者的肺功能随时间的下降情况、囊肿占据的肺容积（囊肿评分）以及囊肿附近的肺组织纹理进行量化。然后我们将西罗莫司的最后一项研究中的囊肿评分与西罗莫司治疗的研究结果进行比较。在12例患者中，我们评估了停用和使用西罗莫司时肺功能和囊肿评分的变化率。
西罗莫司降低了第一秒用力呼气容积（FEV1）的年下降率（预测值的-2.3±0.1%对1.0±0.3%；P<0.001）和一氧化碳弥散量（预测值的-2.6±0.1%对0.9±0.2%；P<0.001）。开始使用西罗莫司后1.2±0.8年（30.5±11.9%）和2.5±2年（29.7±12.1%）的囊肿评分与治疗前值（28.4±12.5%）无显著差异。在随访5年的12例患者中，观察到FEV1年下降率显著降低（预测值的-1.4±0.2%对0.3±0.4%；P=0.025）。对104次计算机断层扫描的分析显示，囊肿评分（1.8±0.2%对0.3±0.3%；P=0.23）和肺纹理特征的年变化率无显著降低（P=0.23）。尽管有不良事件，但大多数患者能够继续使用西罗莫司治疗。
西罗莫司治疗减缓了肺功能下降和囊性病变增加。大多数患者能够耐受西罗莫司治疗。
