Abstract
Previous studies have indicated an association between neutrophil extracellular traps (NETs) and acute respiratory distress syndrome (ARDS). This study aimed to investigate the potential causal effects of NETs and NETs-related biomarkers on ARDS or vice-versa. A two-sample Mendelian randomization (MR) utilizing genome-wide association studies (GWAS) data was employed to analyze the causality. The primary analysis was conducted using inverse-variance weighted (IVW) methods; weighted median, MR-Egger, and weighted model methods were used to validate the results. Horizontal pleiotropy and outlier detection were assessed via MR-Egger and MR pleiotropy residual sum and outlier (MR-PRESSO), respectively; Cochran's Q test evaluated heterogeneity, while Leave-one-out analyses were used to evaluate the presence of predominant instrumental variables (IVs). IVW method suggested causal associations between genetically predicted IL-13 and a higher risk of ARDS [OR (95%CI) = 1.52 (1.03-2.23), P = 0.047], while there was no causal effect of other factors on ARDS (all P > 0.05). Also, ARDS had no effect on NETs and NETs-related biomarkers (all P > 0.05). Cochran's Q confirmed no significant heterogeneity. MR-Egger regression ruled out horizontal pleiotropy's influence, and MR-PRESSO analysis identified no outliers, reinforcing the study's findings. This MR study established a causal relationship between IL-13 and ARDS, suggesting its potential role as a therapeutic target and biomarker of ARDS. Future work should delve into the underlying mechanisms and clinical applications.