Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Chest. 2023 Jul;164(1):137-148. doi: 10.1016/j.chest.2023.02.026. Epub 2023 Feb 18.
Lymphangioleiomyomatosis is a progressive diffuse cystic lung disease with approximately 85% survival at 10 years. The determinants of disease progression and mortality after the introduction of sirolimus therapy and vascular endothelial growth factor D (VEGF-D) as a biomarker have not been well defined.
Which factors, including VEGF-D and sirolimus therapy, influence disease progression and survival prognosis in patients with lymphangioleiomyomatosis?
The progression dataset and the survival dataset included 282 and 574 patients, respectively, from Peking Union Medical College Hospital, Beijing, China. A mixed-effects model was used to compute the rate of decline in FEV, and generalized linear models were used to identify variables affecting FEV decline. A Cox proportional hazards model was used to explore the association between clinical variables and the outcomes of death or lung transplantation in patients with lymphangioleiomyomatosis.
VEGF-D levels and sirolimus treatment were associated with FEV changes and survival prognosis. Compared with patients with VEGF-D of < 800 pg/mL at baseline, patients with VEGF-D of ≥ 800 pg/mL lost FEV faster (SE, -38.86 mL/y; 95% CI, -73.90 to -3.82 mL/y; P = .031). The 8-year cumulative survival rates of patients with VEGF-D of ≥ 2,000 pg/mL and < 2,000 pg/mL were 82.9% and 95.1%, respectively (P = .014). The generalized linear regression model also demonstrated the benefit of delaying the decline of FEV by 65.56 mL/y (95% CI, 29.06-102.06 mL/y) in patients treated with sirolimus compared with those without sirolimus (P < .001). The 8-year risk of death was reduced by 85.1% (hazard ratio, 0.149; 95% CI, 0.075-0.299) after sirolimus treatment. After inverse treatment probability weighting, the risks of death in the sirolimus group were reduced by 85.6%. CT scan results of grade III severity were associated with worse progression than results of grades I or II severity. Patients with baseline FEV of 70% predicted or St. George's Respiratory Questionnaire Symptoms domain 50 or higher predicted a higher risk of worse survival.
Serum VEGF-D levels, a biomarker of lymphangioleiomyomatosis, are associated with disease progression and survival. Sirolimus therapy is associated with slower disease progression and better survival in patients with lymphangioleiomyomatosis.
ClinicalTrials.gov; No.: NCT03193892; URL: www.
gov.
淋巴管平滑肌瘤病是一种进行性弥漫性囊性肺疾病，10 年后的生存率约为 85%。在西罗莫司治疗和血管内皮生长因子 D（VEGF-D）作为生物标志物引入后，疾病进展和死亡率的决定因素尚未得到很好的定义。
哪些因素，包括 VEGF-D 和西罗莫司治疗，会影响淋巴管平滑肌瘤病患者的疾病进展和生存预后？
本研究的进展数据集和生存数据集分别包含了来自中国北京协和医学院医院的 282 名和 574 名患者。使用混合效应模型计算 FEV 的下降率，使用广义线性模型识别影响 FEV 下降的变量。使用 Cox 比例风险模型探讨临床变量与淋巴管平滑肌瘤病患者死亡或肺移植结局之间的关系。
VEGF-D 水平和西罗莫司治疗与 FEV 变化和生存预后相关。与基线时 VEGF-D<800pg/mL 的患者相比，VEGF-D≥800pg/mL 的患者 FEV 下降更快（SE，-38.86mL/y；95%CI，-73.90 至-3.82mL/y；P=0.031）。VEGF-D≥2000pg/mL 和 VEGF-D<2000pg/mL 的患者 8 年累积生存率分别为 82.9%和 95.1%（P=0.014）。广义线性回归模型还表明，与未接受西罗莫司治疗的患者相比，接受西罗莫司治疗的患者 FEV 下降速度可延缓 65.56mL/y（95%CI，29.06-102.06mL/y）（P<0.001）。接受西罗莫司治疗后，患者死亡风险降低了 85.1%（风险比，0.149；95%CI，0.075-0.299）。经过逆治疗概率加权后，西罗莫司组的死亡风险降低了 85.6%。严重程度为 III 级的 CT 扫描结果与进展恶化相关，严重程度为 I 级或 II 级的结果则相反。基线时 FEV 预测值为 70%或圣乔治呼吸问卷症状域 50 分或更高的患者，其生存预后恶化的风险更高。
淋巴管平滑肌瘤病的血清 VEGF-D 水平是一种生物标志物，与疾病进展和生存相关。西罗莫司治疗与淋巴管平滑肌瘤病患者的疾病进展减缓及生存改善相关。
ClinicalTrials.gov；编号：NCT03193892；网址：www.clinicaltrials.gov。
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