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

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 (ß = -0.15, p = 0.003), RV/TLC (ß = 0.09, p = 0.05) and DL, CO (ß = -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.

Matrix Metalloproteinases in COPD and atherosclerosis with emphasis on the effects of smoking.

BACKGROUND: Matrix metalloproteinases (MMP´s) are known biomarkers of atherosclerosis. MMP´s are also involved in the pathophysiological processes underlying chronic obstructive pulmonary disease (COPD). Cigarette smoking plays an important role in both disease states and is also known to affect the concentration and activity of MMP´s systemically. Unfortunately, the epidemiological data concerning the value of MMP´s as biomarkers of COPD and atherosclerosis with special regards to smoking habits are limited. METHODS: 450 middle-aged subjects with records of smoking habits and tobacco consumption were examined with comprehensive spirometry, carotid ultrasound examination and biomarker analysis of MMP-1, -3, -7, -10 and -12. Due to missing data 33 subjects were excluded. RESULTS: The remaining 417 participants were divided into 4 different groups. Group I (n = 157, no plaque and no COPD), group II (n = 136, plaque but no COPD), group III (n = 43, COPD but no plaque) and group IV (n = 81, plaque and COPD). Serum levels of MMP-1,-7,-10-12 were significantly influenced by smoking, and MMP-1, -3, -7 and-12 were elevated in subjects with COPD and carotid plaque. This remained statistically significant for MMP-1 and-12 after adjusting for traditional risk factors. CONCLUSION: COPD and concomitant plaque in the carotid artery were associated with elevated levels of MMP-1 and -MMP-12 even when adjusting for risk factors. Further studies are needed to elucidate if these two MMP´s could be useful as biomarkers in a clinical setting. Smoking was associated with increased serum levels of MMP´s (except for MMP-3) and should be taken into account when interpreting serum MMP results.