Lymphangioleiomyomatosis: Circulating Levels of FGF23 and Pulmonary Diffusion

Authors

Anthony J Esposito
Jewel Imani
Shikshya Shrestha
Shefali Bagwe
Anthony M Lamattina
Marina Vivero
Hilary J Goldberg
Ivan O Rosas
Elizabeth P Henske
Souheil Y El-Chemaly

Publication Date

1-1-2023

Journal

Jornal Brasileiro de Pneumologia

DOI

10.36416/1806-3756/e20220356

PMID

37132737

PMCID

PMC10171272

PubMedCentral® Posted Date

4-17-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Lymphangioleiomyomatosis, Retrospective Studies, Lung Diseases, Biomarkers, Lung, Lung Neoplasms, Lymphangioleiomyomatosis, Fibroblast growth factor-23, Pulmonary diffusing capacity

Abstract

OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare, destructive disease of the lungs with a limited number of determinants of disease activity, which are a critical need for clinical trials. FGF23 has been implicated in several chronic pulmonary diseases. We aimed to determine the association between serum FGF23 levels and pulmonary function in a cohort of patients with LAM.

METHODS: This was a descriptive single-center study in which subjects with LAM and controls with unreported lung disease were recruited. Serum FGF23 levels were measured in all subjects. Clinical data, including pulmonary function testing, were retrospectively obtained from electronic medical records of LAM subjects. Associations between FGF23 levels and clinical features of LAM were explored via nonparametric hypothesis testing.

RESULTS: The sample comprised 37 subjects with LAM and 16 controls. FGF23 levels were higher in the LAM group than in the control group. In the LAM group, FGF23 levels above the optimal cutoff point distinguished 33% of the subjects who had nondiagnostic VEGF-D levels. Lower FGF23 levels were associated with impaired DLCO (p = 0.04), particularly for those with isolated diffusion impairment with no other spirometric abnormalities (p = 0.04).

CONCLUSIONS: Our results suggest that FGF23 is associated with pulmonary diffusion abnormalities in LAM patients and elicit novel mechanisms of LAM pathogenesis. FGF23 alone or in combination with other molecules needs to be validated as a biomarker of LAM activity in future clinical research.