Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Cincinnati College of Medicine and the Cincinnati Veteran's Affairs Medical Center, Cincinnati, OH, USA.
Lung. 2013 Feb;191(1):35-42. doi: 10.1007/s00408-012-9419-3. Epub 2012 Sep 25.
Lymphangioleiomyomatosis (LAM) is a rare, progressive, frequently lethal cystic lung disease that almost exclusively affects women. Prognostic information in LAM has been limited by small numbers and heterogeneous study methodology. Early retrospective cohorts cited 5- and 10-year mortality of 40 and 80 %, respectively. More recently, mortality at 10 years has been estimated to be approximately 10-20 % from the onset of symptoms and 30 % at 10 years from the time of lung biopsy but varies widely in individual patients. Given the heterogeneous disease course, it would be useful to establish which clinical characteristics are associated with survival to develop prediction models for disease outcome.
The LAM Foundation maintains a population-based registry of 1,149 registered self-identified LAM patients. Of these, 590 have completed a "General Information/Clinical History Questionnaire" with limited demographic and clinical data, 410 of whom were identified as U.S. residents and provided date of birth. Vital status was obtained on all 410 participants through December 31, 2007 by linking patient identifiers and the National Death Index. Survival time was calculated as the time since first lung-related symptom or physician diagnosis until censoring (still alive, received lung transplant, or died). Cox proportional hazard analysis evaluated the association of demographic and clinical features with survival.
Among the 410 subjects, there were 50 deaths and 55 lung transplantations during a median of 10.4 years of observation time. The estimated median transplant-free survival time for LAM patients in the United States is 29 years from symptom onset and 23 years from diagnosis. The estimated 10-year survival transplant-free was 86 %. Age at disease onset, smoking status, race, presence of tuberous sclerosis, occurrence of pneumothorax, and pregnancy did not demonstrate an association with survival or transplant. Greater age at presentation and presence of angiomyolipoma were associated with less risk of mortality. Treatment with hormonal therapy was associated with an increased risk of death/transplant (hazard ratio (HR) 2.93; 95 % confidence interval (CI), 1.54-5.58; p = 0.001), particularly progesterone therapy (HR 2.17; 95 % CI 1.26-3.75, p = 0.005), and may represent confounding by indication. Patients who required oxygen therapy had a worse outcome (HR 4.53; 95 % CI 2.76-7.42; p < 0.001).
Our population-based study showed that the median survival in patients with LAM from the onset of symptoms or diagnosis is much longer than previously described. This has important implications for life choices and treatment decisions regarding medication use and lung transplantation for patients with LAM.
淋巴管平滑肌瘤病（LAM）是一种罕见的、进行性的、常致命的囊性肺部疾病，几乎仅影响女性。LAM 的预后信息受到数量有限和研究方法异质性的限制。早期回顾性队列研究报告的 5 年和 10 年死亡率分别为 40%和 80%。最近，从症状出现到 10 年的死亡率估计约为 10-20%，从肺活检到 10 年的死亡率为 30%，但在个体患者中差异很大。鉴于疾病过程存在异质性，如果能够确定哪些临床特征与生存相关，将有助于建立预测疾病结局的预测模型。
LAM 基金会维护着一个基于人群的登记处，其中包括 1149 名自我识别的 LAM 患者。其中，590 名患者完成了一份“一般信息/临床病史问卷”，其中包含有限的人口统计学和临床数据，其中 410 名患者被确定为美国居民，并提供了出生日期。通过将患者标识符与国家死亡索引相链接，在 2007 年 12 月 31 日之前，对所有 410 名参与者的生存状态进行了追踪。生存时间从首次肺部相关症状或医生诊断开始计算，直到截尾（仍存活、接受肺移植或死亡）。Cox 比例风险分析评估了人口统计学和临床特征与生存的关系。
在 410 名受试者中，有 50 人死亡，55 人接受了肺移植，中位观察时间为 10.4 年。在美国，LAM 患者的中位无移植生存时间从症状出现到诊断分别为 29 年和 23 年。估计的 10 年无移植生存率为 86%。发病年龄、吸烟状况、种族、是否存在结节性硬化症、气胸发生情况和妊娠与生存或移植均无相关性。发病时年龄较大和存在血管平滑肌脂肪瘤与较低的死亡率风险相关。激素治疗与死亡/移植风险增加相关（风险比（HR）2.93；95%置信区间（CI），1.54-5.58；p=0.001），特别是孕激素治疗（HR 2.17；95%CI 1.26-3.75，p=0.005），这可能是由于指示性偏倚所致。需要氧疗的患者预后较差（HR 4.53；95%CI 2.76-7.42；p<0.001）。
我们的基于人群的研究表明，从症状出现或诊断开始，LAM 患者的中位生存时间明显长于之前描述的时间。这对于 LAM 患者的药物使用和肺移植治疗的生活选择和治疗决策具有重要意义。
