The Causal Role of Immune Cell Phenotypes and Inflammatory Factors in Childhood Asthma: Evidence From Mendelian Randomization

作者：Zhoushan Feng, Chunhong Jia, Bing Han, Xiaochun Chen, Jingwen Mei, Shicun Qiao, Xiaohong Wu, Fan Wu · 发表于：Pediatric Pulmonology · 年份：2025 · DOI：10.1002/ppul.27480 · 被引用次数：4 · 研究领域：Asthma and respiratory diseases、Genetic Associations and Epidemiology、IL-33, ST2, and ILC Pathways

OBJECTIVE: This study utilizes Mendelian randomization (MR) to explore the causal relationship between immune cell phenotypes, inflammatory factors, and childhood asthma, aiming to enhance our understanding and management of the disease. METHODS: A two-sample MR approach was used to explore the causal relationships between 731 immune cell phenotypes, 91 inflammatory factors, and childhood asthma. The main analysis was performed using inverse variance weighting (IVW), with additional methods like weighted median, MR-Egger, and weighted mode. Statistical significance was further assessed using false discovery rate (FDR) correction. Sensitivity analyses assessed heterogeneity (Cochran's Q test) and pleiotropy (MR-Egger, MR-PRESSO), while reverse causality was evaluated using the Steiger test. Findings were further validated through cohort studies and meta-analyses to ensure robustness. RESULTS: Among 91 inflammatory factors, DNER, IL-18 R1, and Osteoprotegerin increased childhood asthma risk, while CDCP1 and VEGF-A were protective (p < 0.05). Of 731 immune cell phenotypes, 45 showed significant links to asthma, with protective effects from CD45RA+ CD8+ T cells and HLA-DR+ NK cells, and increased risk from IgD-CD38- B cells and CD8dim T cells (p < 0.05). Specific SSC-A parameters and higher MFI values for CD19, CD28, and CD3 were protective, while elevated MFI for CCR2 on monocytes and CD86 on myeloid dendritic cells increased risk. However, after further FDR correction, no stati...