Could Hepcidin Be a Phenotype-Related Biomarker in Patients with Stable Bronchiectasis?

Hepcidin centrally regulates iron homeostasis and responds to inflammation, iron status, hypoxia, and erythropoietic signaling, yet circulating hepcidin in stable bronchiectasis is poorly characterized. We compared serum hepcidin between 61 patients with stable bronchiectasis and 39 controls without bronchiectasis and assessed associations with anemia, iron metabolism, systemic inflammation, severity, and phenotype. Hepcidin was lower in bronchiectasis (20.34 ± 7.85 vs. 28.34 ± 9.82 ng/mL; median, 20.31 [15.07-25.35] vs. 25.03 [21.00-34.66] ng/mL; p < 0.001). It showed no significant associations with anemia status or hematologic, iron metabolism, erythropoietic, or inflammatory indices. Exploratory analyses identified phenotype differences (p = 0.002); levels were lowest in chronic obstructive pulmonary disease-bronchiectasis (15.98 ± 6.52 ng/mL), compared with bronchiectasis alone (21.57 ± 6.71) and asthma-bronchiectasis (24.81 ± 9.00). Low hepcidin discriminated bronchiectasis from controls (AUC = 0.729; 95% bootstrap CI: 0.628-0.822); the ≤20.85 ng/mL cutoff yielded 59.0% sensitivity and 79.5% specificity. To our knowledge, this is the first human case-control evidence of reduced circulating hepcidin in stable bronchiectasis. The absence of significant associations with systemic inflammation or anemia/iron status, alongside phenotype differences, suggests that hepcidin may be a candidate biomarker of biological heterogeneity in bronchiectasis not reflected by routine markers.