Elevated plasma eosinophil-derived neurotoxin is associated with echocardiographic pulmonary vascular involvement in stable COPD.

BACKGROUND

Pulmonary vascular involvement is an important dimension of chronic obstructive pulmonary disease (COPD) heterogeneity, but its biological features may not be fully represented by airflow limitation, gas-transfer impairment, or resting hypoxemia. eosinophil-derived neurotoxin (EDN) is a circulating eosinophil-derived protein whose relationship with pulmonary vascular involvement in stable COPD is unknown.

METHODS

This single-center observational cohort study included 53 clinically stable participants with COPD and 10 healthy controls. COPD participants were classified by echocardiographic pulmonary vascular involvement (n = 10) or its absence (n = 43). Right-heart catheterization was not used for group assignment. EDN was measured in EDTA plasma by enzyme-linked immunosorbent assay. The primary analysis estimated the adjusted EDN difference between COPD groups using ordinary least-squares regression with HC3 robust standard errors. Covariates were age, sex, forced expiratory volume in 1 s, diffusing capacity for carbon monoxide, and room-air arterial oxygen tension. Secondary models examined adjusted associations with tricuspid regurgitation (TR) pressure gradient and echocardiographic pulmonary artery-to-aorta ratio (PA/Ao).

RESULTS

Median plasma EDN was 181.58 ng/mL (interquartile range [IQR], 164.98-202.53) in participants with echocardiographic pulmonary vascular involvement and 125.66 ng/mL (IQR, 113.14-140.54) in those without such involvement. The adjusted group difference was 48.93 ng/mL (95% CI, 30.04-67.81; P < 0.001). Secondary slopes were positive for TR pressure gradient (0.86 ng/mL per mmHg; 95% CI, 0.07-1.65; nominal P = 0.033) and PA/Ao (93.40 ng/mL per unit; 95% CI, 9.71-177.09; nominal P = 0.030); Holm-adjusted P = 0.059 for both. Leave-one-case-out estimates ranged from 44.59 to 53.37 ng/mL, with every lower 95% confidence bound above zero.

CONCLUSION

After adjustment for measured respiratory variables, plasma EDN was higher in stable COPD with echocardiographic pulmonary vascular involvement. The corresponding patterns observed for TR pressure gradient and PA/Ao provide additional rationale for evaluating EDN in external cohorts with standardized echocardiography, paired eosinophil measurements, and invasive hemodynamic assessment.