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. 2019 Feb;155(2):288-296.
doi: 10.1016/j.chest.2018.06.016. Epub 2018 Jun 22.

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

Nishant Gupta  1 , Hye-Seung Lee  2 , Jay H Ryu  3 , Angelo M Taveira-DaSilva  4 , Gerald J Beck  5 , Jar-Chi Lee  5 , Kevin McCarthy  6 , Geraldine A Finlay  7 , Kevin K Brown  8 , Stephen J Ruoss  9 , Nilo A Avila  10 , Joel Moss  4 , Francis X McCormack  11 ; NHLBI LAM Registry Group
Affiliations

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

Nishant Gupta et al. Chest. 2019 Feb.

Abstract

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.

Keywords: VEGF-D; menopause; natural history; pulmonary function tests; tuberous sclerosis complex.

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Figures

Figure 1
Figure 1
FEV1 decline over time in the National Heart, Lung, and Blood Institute (NHLBI) Registry Cohort.
Figure 2
Figure 2
Kaplan-Meier curve showing death/transplantation as outcome from the time of diagnosis. LAM = lymphangioleiomyomatosis.
Figure 3
Figure 3
Kaplan-Meier curve showing death/transplantation as outcome after segregating patients into premenopausal and postmenopausal status at their baseline visit. Postmenopausal subjects had a lower risk of progression to death or lung transplantation compared with the premenopausal subjects.
Figure 4
Figure 4
Kaplan-Meier curve showing death/transplantation as an outcome after segregating patients on the basis of their initial FEV1 values. Higher baseline FEV1 was associated with a decreased risk of progression to death or lung transplantation.
Figure 5
Figure 5
Kaplan-Meier curve showing death/transplantation as outcome after segregating patients based on their initial Dlco values. Higher baseline Dlco was associated with a decreased risk of progression to death or lung transplantation. Dlco = diffusion capacity of lung for carbon monoxide.
See this image and copyright information in PMC

Comment in

References

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