Air Pollution-Associated Intracellular Metals, Immune Gene Expression, and Erythrocyte Indices in COPD with Anemia

Anemia is common in chronic obstructive pulmonary disease (COPD) and may be influenced by air pollution-related metal accumulation. However, the biological links among air pollution, intracellular metals, immune gene expression, and erythrocyte alterations remain unclear.

We examined associations between air pollutants, intracellular metals, gene expression, and erythrocyte indices in sixty-one COPD patients and ten healthy controls. Annual exposures to particulate matter with aerodynamic diameter ≤10 µm (PM₁₀), ≤2.5 µm (PM_2.5), nitrogen dioxide (NO₂), and nitrogen oxides (NOx) were estimated using land use regression. Metals were quantified by inductively coupled plasma mass spectrometry (ICP-MS) and single-cell ICP-MS. Gene expression in peripheral blood mononuclear cells (PBMCs) was profiled by RNA sequencing.

In COPD, PM_2.5 was associated with higher red blood cell (RBC) count (β = 0.0314×10⁶ cells/µL; 95% confidence interval (CI): 0.0066 ~ 0.0561) and ln(red cell distribution width) (β = 0.0051; 95% CI: 0.0003 ~ 0.0098). PM_2.5 was also associated with higher ln(chromium (Cr)) in PBMCs (β = 0.0632; 95% CI: 0.0124 ~ 0.1139), ln(zinc (Zn)) in RBCs (β = 0.1338; 95% CI: 0.0388 ~ 0.2288), and ln(cadmium (Cd)) in RBCs (β = 0.1297; 95% CI: 0.0125 ~ 0.2469). RBC Cr, Cd, lead, and vanadium were positively associated with hemoglobin, hematocrit, and mean corpuscular volume. In PBMCs, Cr, Cd, Zn, and single-cell iron were associated with ALPL, CXCR1, and PI3 expression. Anemic COPD patients showed upregulation of IFI27 and TRAV38-1 and downregulation of DEFA1, PI3, CXCR1, and ALPL.

Intracellular metals, particularly Cr and Cd, were associated with immune-related gene expression profiles and anemia-related erythrocyte indices in COPD. These findings suggest potential biological associations among air pollution exposure, intracellular metal burden, immune dysregulation, and hematologic alterations in COPD.