Air pollution and oxidative stress in adults suffering from airway diseases. Insights from the Gene Environment Interactions in Respiratory Diseases (GEIRD) multi-case control study

Air pollution is a leading risk factor for global mortality and morbidity. Oxidative stress is a key mechanism underlying air-pollution-mediated health effects, especially in the pathogenesis/exacerbation of airway impairments. However, evidence lacks on subgroups at higher risk of developing more severe outcomes in response to air pollution. This multi-centre study aims to evaluate the association between air pollution and oxidative stress in healthy adults and in patients affected by airway diseases from the Italian GEIRD (Gene Environment Interactions in Respiratory Diseases) multi-case control study. Overall, 1841 adults (49 % females, 20-83 years) were included from four Italian centres: Pavia, Sassari, Turin, and Verona. Following a 2-stage screening process, we identified 1273 cases of asthma, chronic bronchitis, rhinitis, or COPD and 568 controls. Systemic oxidative stress was quantified by urinary 8-isoprostane and 8-OH-dG. Individual residential exposures to NO₂, PM₁₀, PM_2.5, and O₃ were derived using an innovative five-stage machine-learning-based approach. Linear mixed regression models tested the association between oxidative stress biomarkers and air pollution tertiles, adjusting by age, sex, BMI, smoking, education and season, with recruiting centres as random intercept. Only cases exhibited higher levels of log-transformed 8-isoprostane and 8-OH-dG in association with NO₂ (β: 0.30 95 % CI: 0.08-0.52 and 0.20 95 % CI: 0.03-0.37), PM₁₀ (0.34 95 % CI: 0.12-0.55 and 0.21 95 % CI: 0.05-0.37) and PM_2.5 (0.27 95 % CI: 0.09-0.49 and 0.18 95 % CI: 0.02-0.34) as compared to the first tertile of exposure. No significant associations were observed for summer O₃. Our findings suggest that exposure to air pollution may increase systemic oxidative stress levels in people suffering from airway diseases. This introduces a potential novel approach available for future epidemiological studies and Public Health for effective prevention strategies oriented at the quantification of early biological effects in susceptible people, whose additional risk level might be currently underrated. Air-pollution-mediated exacerbations, driven by oxidative stress, still deserve our attention.