The role of eosinophil and neutrophil counts in mediating the effect of asthma on chronic obstructive pulmonary disease: a mendelian randomization study

Asthma is linked to increase the risk of chronic obstructive pulmonary disease (COPD), but the causal relationship remains uncertain due to confounding factors. Eosinophilic and neutrophilic inflammation are known pathways connecting asthma and COPD. However, the extent to which these pathways causally mediate the transition has not been genetically quantified. This study applies a two-sample Mendelian randomization (MR) framework to genetically assess the causal effect of asthma on COPD and to quantify the role of airway inflammatory cells in this relationship. Genetic predisposition to asthma was associated with increased COPD risk (OR: 1.27, 95% CI: 1.16–1.40) and higher levels of eosinophils, neutrophils, and basophils. Elevated eosinophil and neutrophil counts were independently linked to increased COPD susceptibility. MR mediation analysis revealed that eosinophils and neutrophils explained 6.56% and 0.66% of the total effect, respectively. After adjusting for both mediators, the direct effect of asthma on COPD strengthened (OR: 1.42, 95% CI: 1.27–1.59), indicating additional non-inflammatory pathways. These results support a causal role of asthma in COPD pathogenesis, with partial mediation by eosinophilic and neutrophilic inflammation. Inflammation control may reduce COPD risk but cannot fully prevent or explain its onset.