Previous studies have explored the connection between the dietary inflammation index (DII) and asthma-COPD Overlap (ACO)
however, the relationship between diet and the risk of ACO from an antioxidant perspective remains unexamined. We hypothesized that a proinflammatory diet may increase the risk of ACO by promoting inflammation, whereas an antioxidant diet may reduce the risk by mitigating inflammation. To test this hypothesis, we conducted a cross-sectional study utilizing data from the National Health and Nutrition Examination Survey (NHANES) in 2003-2018, including 23,050 participants. The study employed propensity score matching (PSM), logistic regression, restricted cubic splines (RCS), and mediation analysis. Pre-PSM and post-PSM RCS analyses indicated a positive correlation between DII and ACO, while the composite dietary antioxidant index (CDAI) demonstrated a negative association (P-overall <
0 .05). Pre-PSM and post-PSM logistic regression results showed that higher DII scores were associated with an increased risk of ACO, while higher CDAI scores correlated with a reduced risk of ACO (P <
0 .05). Mediation analysis further indicated that pro-inflammatory diets increased ACO risk through elevated levels of white blood cells (WBC), eosinophil counts (EC), systemic immune-inflammation index (SII), and system inflammation response index (SIRI) (P <
0.05). In contrast, antioxidant diets reduced the risk of ACO events by decreasing the levels of these inflammatory markers (P <
0.05). In conclusion, higher DII scores may increase the risk of ACO, while higher CDAI scores may decrease it. Both DII and CDAI mediate their effects through inflammatory markers, including WBC, EC, SII, and SIRI.