The NHLBI LAM Registry: Prognostic Physiologic and Radiologic Biomarkers Emerge From a 15-Year Prospective Longitudinal Analysis

Background: The natural history of lymphangioleiomyomatosis (LAM) is mainly derived from retrospective cohort analyses, and it remains incompletely understood. A National Institutes of Health LAM Registry was established to define the natural history and identify prognostic biomarkers that can help guide management and decision-making in patients with LAM. Methods: A linear mixed effects model was used to compute the rate of decline of FEV₁ and to identify variables affecting FEV₁ decline among 217 registry patients who enrolled from 1998 to 2001. Prognostic variables associated with progression to death/lung transplantation were identified by using a Cox proportional hazards model. Results: Mean annual decline of FEV₁ was 89 ± 53 mL/year and remained remarkably constant regardless of baseline lung function. FEV₁ decline was more rapid in those with greater cyst profusion on CT scanning (P =.02) and in premenopausal subjects (118 mL/year) compared with postmenopausal subjects (74 mL/year) (P =.003). There were 26 deaths and 43 lung transplantations during the evaluation period. The estimated 5-, 10-, 15-, and 20-year transplant-free survival rates were 94%, 85%, 75%, and 64%, respectively. Postmenopausal status (hazard ratio, 0.30; P =.0002) and higher baseline FEV₁ (hazard ratio, 0.97; P =.008) or diffusion capacity of lung for carbon monoxide (hazard ratio, 0.97; P =.001) were independently associated with a lower risk of progression to death or lung transplantation. Conclusions: The median transplant-free survival in patients with LAM is > 20 years. Menopausal status, as well as structural and physiologic markers of disease severity, significantly affect the rate of decline of FEV₁ and progression to death or lung transplantation in LAM.