Fibroblast growth factor 23 is an independent marker of COPD and is associated with impairment of pulmonary function and diffusing capacity

M Kraen,S Frantz,U Nihlén,G Engström,C.G Löfdahl,P Wollmer,M Dencker

doi:10.1016/j.rmed.2021.106404

M Kraen, S Frantz + Show 5 more

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https://doi.org/10.1016/j.rmed.2021.106404

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Journal: Respiratory Medicine	Publication Date: Apr 17, 2021
Citations: 7	License type: cc-by

Affiliation: Lund University

Abstract

Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that in recent years has been reported to have significant effects on numerous tissues. Chronic obstructive pulmonary disease (COPD) is associated with hypophosphatemia but the evidence for elevated plasma levels of FGF23 in COPD subjects is ambiguous. Recently, FGF23 has even been shown to be involved in the inflammatory pathways activated in COPD, so FGF23 could be a novel biomarker for COPD and impairment of pulmonary function.The purpose was thus to explore the association of FGF23 with COPD and measures of pulmonary function.This was a cross sectional study of 450 subjects who underwent spirometry, body plethysmography, determination of diffusing capacity (DL,CO) and biomarker analysis of FGF23, interleukin (IL)-1 receptor antagonist, IL-6 and IL-8. Forty-four participants were excluded due to missing data or renal impairment (eGFR <45 mL/min/m2).Spirometry identified 123 subjects with COPD. FGF23 levels were elevated in COPD subjects compared to non COPD subjects, and this remained significant after adjustment for age, sex and smoking habits (OR = 1.6, p = 0.02). Linear regression showed significant relationships between FGF23 and FEV1 (β = −0.15, p = 0.003), RV/TLC (β = 0.09, p = 0.05) and DL, CO (β = −0.24, p < 0.001).In conclusion we found that plasma levels of FGF23 are elevated in COPD subjects even when adjusting for traditional risk factors. Furthermore, FGF23 is associated with impairment in lung function as measured by FEV1 and DL,CO. Further studies are needed to establish whether FGF23 could serve as a novel biomarker of COPD and emphysema development.

Highlights

Fibroblast growth factor 23 (FGF23) is a bone derived hormone responsible for regulating phosphate metabolism and its synthesis is governed by blood phosphate levels
The final study group consisted of 406 participants who were sub sequently divided into a chronic obstructive pulmonary disease (COPD) group (n = 117) and a non-COPD group (n = 289) based on the spirometry findings
FGF23 was elevated in COPD subjects while IL-1 receptor antagonist (IL-1ra), IL-6 and IL-8 levels were unaffected by group status

Summary

Introduction

Fibroblast growth factor 23 (FGF23) is a bone derived hormone responsible for regulating phosphate metabolism and its synthesis is governed by blood phosphate levels. It is known that the lung expresses all four FGF23 receptors and it has recently been reported that human bronchial epithelial cells can release IL-1beta via FGFR4 in a KL inde pendent fashion in response to exposure to cigarette smoke and FGF23 [9]. Α-klotho protects against inflammation and oxidative damage in alveolar and bronchial epithelial cells [9,13] and it has recently been shown that KL expression is down regulated in chronic obstructive pulmonary disease (COPD) subjects [14] and after exposure to cigarette smoke [9]. The purpose of the present study was to explore whether FGF23 was elevated in subjects with COPD without significant chronic kidney disease, and if it was associ ated with measures of impaired pulmonary function

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