Circulating fibronectin to C-reactive protein ratio and mortality: a biomarker in COPD?

Abstract

The balance between inflammatory and repair processes is important in maintaining lung homeostasis in chronic obstructive pulmonary disease (COPD). The aim of the present study was to determine whether or not an integrated index of a biomarker involved in inflammation, C-reactive protein (CRP), and another involved in wound repair, fibronectin, may be a good measure to predict clinical outcomes in COPD.Circulating blood levels of CRP and fibronectin were measured in 4,787 individuals with mild-tomoderate COPD who were prospectively followed for .7 yrs after blood collection as part of the Lung Health Study. To assess the balance between repair and inflammation, a simple ratio was calculated by dividing fibronectin levels by CRP levels and a Cox proportional hazards model was used to determine the relationship between this ratio and all-cause and disease-specific causes of mortality.The relationship between the fibronectin to CRP ratio and all-cause mortality was L-shaped. There was an exponential decay in the adjusted hazard function (i.e. the risk of mortality) as the ratio decreased until a value of 148 was reached, beyond which point the hazard function did not change significantly. Similar results were observed for the risk of coronary and cardiovascular mortality.Circulating fibronectin to CRP ratio is significantly associated with all-cause mortality of COPD patients. However, in contrast to other biomarkers, the relationship appears to be L-shaped (and not linear), suggesting a threshold at ,150. While promising, future studies are needed to validate this simple index as a biomarker in COPD.

The of COPD: or balancing repair (yang) and inflammation (yin)

“…The research by MAN et al [1] is opportunistic as data were collected for a different purpose in an original clinical trial [5], so the study in the present issue of the ERJ has intrinsic limitations, some of them already highlighted by the authors. As in any cross-sectional analysis, causality cannot be inferred.…”

“…In a ratio of fibronectin to CRP, this could happen either through a higher fibronectin concentration (more repair) or through a lower CRP (less inflammation). Naturally, the study by MAN et al [1] is hypothesis-generating and deserves to be tested in other samples of COPD individuals with a more varied severity and from different settings.…”

“…In this issue of the European Respiratory Journal (ERJ), MAN et al [1] hypothesise that a ratio of fibronectin to C-reactive protein (CRP) is a more suitable tool than each separated biomarker to assess the prognosis of chronic obstructive pulmonary disease (COPD). Using the Lung Health Study III data [2], they updated (and improved on) their previous research on CRP only [3].…”

“…In fact, acute inflammation is the first step of a successful repair process [6] and a clear-cut separation between the two processes is blurred. As MAN et al [1] discuss, measurements were taken at a single time-point, so the reproducibility of this ratio as well as their direct relationship to other important dimensions of the disease has to be explored. In fact, there was no consistency of the reported association with decline in lung function or respiratory-specific mortality (communication from the authors), which is in contradiction with the initial hypothesis.…”

Plasma Fibronectin Concentration in Obese/Overweight Pregnant Women: A Possible Risk Factor for Preeclampsia

“…Changes in the concentration of fibronectin in tissues and body fluids have been reported in various disease conditions. For example elevated levels of fibronectin have been found in plasma of patients with rheumatoid vasculitis [2], collagen vascular diseases, diabetes mellitus [3], chronic obstructive pulmonary disease [4], ischemic heart disease [5], renal cancer [6], gastrointestinal cancer [7], acute myocardiac infarction [8], coronary artery disease [9] and trauma [10]. Increased levels of fibronectin in plasma of patients with some of these conditions were attributed to increased synthesis caused by proinflammatory cytokines, and release of extracelluar matrix and cell surface fibronectins into circulating plasma [3].…”