Association Between Serum Growth Factors and Risk of Acute Exacerbation in Chronic Obstructive Pulmonary Disease: A One-Year Prospective Study

TL;DR

This study found that lower levels of certain growth factors in the blood are linked to a higher risk of COPD flare-ups, suggesting potential biomarkers for predicting disease worsening.

Contribution

Identifies serum fibroblast growth factor-2 (FGF-2) and nerve growth factor (NGF) as potential biomarkers for predicting COPD exacerbation risk.

Findings

Lower serum FGF-2 levels were significantly associated with increased acute exacerbation risk in COPD patients.

Lower NGF levels strongly predicted frequent COPD exacerbations with high discriminatory power.

FGF-2 ≤ 9.12 pg/mL and NGF ≤ 25.23 pg/mL were identified as potential thresholds for exacerbation prediction.

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation associated with enhanced chronic airway inflammation. Growth factors implicated in COPD’s inflammatory processes may serve as biomarkers for disease progression and exacerbation risk. This study evaluated the relationship between serum growth factors and COPD exacerbations over one year. Serum levels of eleven growth factors, including brain-derived neurotrophic factor (BDNF), leukemia inhibitory factor (LIF), fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), nerve growth factor (NGF), epidermal growth factor (EGF), and stem cell factor (SCF), were measured in COPD patients at baseline. Participants were followed prospectively for one year, and associations between these biomarkers and acute exacerbations (AE) and frequent acute exacerbations (Frequent AE) were assessed using statistical analyses and receiver operating characteristic (ROC) curves. Among the study population, 42 patients experienced at least one AE within the follow-up period. Lower serum FGF-2 levels were significantly associated with increased AE risk (adjusted odds ratio significant after covariate adjustment). ROC analysis identified FGF-2 ≤ 9.12 pg/mL as a predictor of AE (AUC = 0.614, sensitivity = 64.3%, specificity = 57.1%, p = 0.032). For Frequent AE, eight patients experienced multiple exacerbations and exhibited significantly lower levels of NGF, EGF, FGF-2, and LIF. After adjustment, NGF remained significantly predictive; NGF ≤ 25.23 pg/mL demonstrated strong discriminatory power for Frequent AE (AUC = 0.797, p < 0.001). However, interpretations are limited by the small Frequent AE subgroup. Serum growth factors, particularly FGF-2 and NGF, are associated with COPD exacerbation risk. Lower serum FGF-2 may indicate a higher likelihood of acute exacerbations, while lower NGF strongly predicts frequent exacerbations. Larger studies and longer follow-ups are needed to confirm these biomarkers’ predictive utility.

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