Chi-Thien Dinh, Jer-Hwa Chang, Tzu-Tao Chen, Ching-Huang Lai, Kuan-Yuan Chen, Po-Hao Feng, Kang-Yun Lee, Chien-Hua Tseng, Huan Minh Tran, Tzu-Hsuen Yuan, Shu-Chuan Ho, Sheng-Ming Wu, Hsiao-Chi Chuang
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.
BACKGROUND: 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.
METHODS: 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 (PM2.5), 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.
RESULTS: In COPD, PM2.5 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). PM2.5 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.
CONCLUSION: 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.