PURPOSE: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.