Soluble Transferrin Receptor-1 in Pulmonary Hypertension Associated with COPD.

Area of Science:

• Pulmonary Medicine
• Cardiovascular Research
• Hematology

Background:

• Chronic obstructive pulmonary disease (COPD) exhibits diverse pulmonary vascular involvement, ranging from mild to severe pulmonary hypertension (PH).
• Iron-dependent regulators, such as hypoxia-inducible factor-2 (HIF-2), are implicated in COPD's phenotypic variations.
• Soluble transferrin receptor-1 (sTfR1) plays a role in iron homeostasis and has emerged as a potential factor in disease pathogenesis.

Purpose of the Study:

• To investigate the diagnostic and prognostic role of soluble transferrin receptor-1 (sTfR1) in pulmonary hypertension (PH) associated with COPD.
• To identify distinct COPD phenotypes based on sTfR1 levels and clinical parameters.
• To explore the relationship between sTfR1, iron deposition, and PH severity in COPD.

Main Methods:

• Analysis of COPD outpatients undergoing right heart catheterization.
• Unsupervised clustering based on sTfR1 levels and non-invasive clinical data to define COPD phenotypes.
• Examination of explanted end-stage COPD lungs for TfR1 expression and iron deposition.

Main Results:

• sTfR1 levels correlated significantly with mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR).
• Elevated sTfR1 was associated with poor survival and predicted severe PH, with improved prediction when combined with low hemoglobin.
• Cluster analysis identified three COPD phenotypes, with two exhibiting poor survival, one characterized by moderate airway obstruction, PH, elevated sTfR1, anemia, and inflammation.
• Explanted lungs showed TfR1-positive, iron-laden cells (likely macrophages), with iron-loaded cell density negatively correlated with mPAP in moderate/severe PH.

Conclusions:

• Elevated sTfR1 serves as a predictor of poor prognosis in COPD patients.
• sTfR1, particularly with low hemoglobin, shows potential as a biomarker for severe PH in COPD.
• This combination may identify a distinct COPD phenotype characterized by systemic inflammation, anemia, and iron deficiency.