A73-12 Decreased Urinary Mitochondrial DNA as a Marker of Increased Emphysema Progression in Female COPD Patients

Background Emphysema, a key feature of chronic obstructive pulmonary disease (COPD), is characterized by progressive alveolar destruction and compromised gas exchange. High-resolution computed tomography (HRCT) is the gold standard for detecting and quantifying emphysema due to its superior sensitivity and precision in lung imaging. Oxidative stress is central to COPD pathogenesis, driving mitochondrial dysfunction and subsequent release of mitochondrial DNA (mtDNA) into circulation and biofluids. Rationale We postulated that the abundance of cell-free mtDNA might reflect emphysema progression. Methods Mitochondrial function was assessed in human lung epithelial cells from COPD patients and healthy controls by whole mitochondrial genome sequencing, quantification of mtDNA damage, TFAM, a key regulator of mitochondrial biogenesis, and mtDNA copy number (mtDNA-CN). In the Losartan Effects on Emphysema Progression (LEEP) cohort, participants were followed from baseline to 48 weeks. Urinary mtDNA-CN (umtDNA-CN) was measured using TaqMan qPCR (mitochondrial tRNALeu normalized to nuclear B2M), and its associations with HRCT-based emphysema change, sex, age, BMI, and smoking status were evaluated. The predictive value of umtDNA-CN for a 10% emphysema change was examined using receiver operating characteristic (ROC) analysis. Results Lung epithelial cells from COPD patients demonstrated mitochondrial abnormalities—including mtDNA mutations, damage, increased TFAM expression, and higher mtDNA-CN—compared to healthy individuals. In the LEEP cohort (n = 100), umtDNA-CN was inversely correlated with emphysema change on HRCT (β = −1.014; r = −0.1959; p = 0.0508). Subgroup analysis revealed the strongest association in females (β = −2.108; r = −0.4006; p = 0.0094), while no significant correlation was observed in males. ROC analysis for 10% emphysema change showed poor overall discriminative ability (AUC = 0.505), but improved performance in females (AUC = 0.674). Conclusion Decreased urinary mtDNA-CN may serve as an indicator of increased emphysema severity, particularly in female COPD patients.