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        <datestamp>2026-09-23T05:44:27Z</datestamp>
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          <dc:title>Supplementary file 1_Elevated plasma eosinophil-derived neurotoxin is associated with echocardiographic pulmonary vascular involvement in stable COPD.docx</dc:title>
          <dc:creator>Xiaochen Hu (3153816)</dc:creator>
          <dc:creator>Fushi Dong (25094317)</dc:creator>
          <dc:creator>Qi Song (121209)</dc:creator>
          <dc:creator>Lu Liu (171341)</dc:creator>
          <dc:creator>Shihuan Yu (22127354)</dc:creator>
          <dc:subject>Foetal Development and Medicine</dc:subject>
          <dc:subject>chronic obstructive pulmonary disease</dc:subject>
          <dc:subject>diffusing capacity</dc:subject>
          <dc:subject>echocardiographic pulmonary vascular involvement</dc:subject>
          <dc:subject>echocardiography</dc:subject>
          <dc:subject>eosinophil-derived neurotoxin</dc:subject>
          <dc:subject>pulmonary circulation</dc:subject>
          <dc:description>Background&lt;p&gt;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.&lt;/p&gt;Methods&lt;p&gt;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).&lt;/p&gt;Results&lt;p&gt;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 &lt; 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.&lt;/p&gt;Conclusion&lt;p&gt;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.&lt;/p&gt;</dc:description>
          <dc:date>2026-09-23T05:44:27Z</dc:date>
          <dc:type>Dataset</dc:type>
          <dc:type>Dataset</dc:type>
          <dc:identifier>10.3389/fmed.2026.1966419.s001</dc:identifier>
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          <dc:rights>CC BY 4.0</dc:rights>
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