Rosser Franziska J, Yue Molin, Han Yueh-Ying, Forno Erick, Qoyawayma Chris, Manni Michelle L, Acosta-Pérez Edna, Canino Glorisa, Chen Wei, Celedón Juan C
Division of Pulmonary Medicine, Department of Pediatrics.
Department of Biostatistics, and.
Ann Am Thorac Soc. 2025 Jun;22(6):872-880. doi: 10.1513/AnnalsATS.202403-309OC.
Little is known about long-term particulate matter 92.5 μm in aerodynamic diameter (PM) exposure and airway epithelial gene expression. To test for association between long-term PM exposure and nasal epithelial gene expression in youth with asthma. Transcriptome-wide association study (TWAS) of long-term PM in nasal epithelium from youth aged 6-20 years in the ) Epigenetic Variation and Childhood Asthma in Puerto Ricans study ( = 182), ) Vitamin D Kids Asthma Study ( = 58), and ) Stress and Treatment Response in Puerto Rican and African American Children with Asthma study ( = 81). Satellite hybrid models were used to estimate PM exposure in the prior year at each participant's residence. Multivariable negative binomial regression was used for each TWAS, adjusting for age, sex, and other covariates. A meta-analysis of all TWAS results was then conducted using an inverse variance-weighted average approach. Most participants (∼95%) in the meta-analysis of TWAS for PM exposure identified as Puerto Rican or Black. Long-term PM was associated with ) upregulated expression of (calcium-activated chloride channel regulator 1; false discovery rate-adjusted [FDR-P] = 0.008), (synaptonemal complex protein 2; FDR-P = 0.01), and (cytochrome p450 family 2 subfamily A member 6; FDR-P = 0.02); and ) downregulated expression of (ectodysplasin A receptor; FDR-P = 0.01). In a meta-analysis, upregulation was associated with one or more positive allergen-specific IgE (FDR-P < 0.001) and increased blood eosinophils (FDR-P < 0.001) and total IgE (FDR-P < 0.001). In a meta-analysis of TWASs in predominantly Puerto Rican and Black youth with asthma, long-term PM exposure was associated with upregulated airway epithelial expression, in turn linked to biomarkers of T2-high immunity.
关于长期暴露于空气动力学直径为92.5微米的颗粒物（PM）与气道上皮基因表达的情况，人们了解甚少。为了测试长期PM暴露与哮喘青少年鼻上皮基因表达之间的关联。在波多黎各裔的表观遗传变异与儿童哮喘研究（n = 182）、维生素D儿童哮喘研究（n = 58）以及波多黎各裔和非裔美国哮喘儿童的应激与治疗反应研究（n = 81）中，对6至20岁青少年鼻上皮中的长期PM进行全转录组关联研究（TWAS）。使用卫星混合模型估计每位参与者住所前一年的PM暴露情况。对每个TWAS使用多变量负二项回归，并对年龄、性别和其他协变量进行调整。然后使用逆方差加权平均法对所有TWAS结果进行荟萃分析。在PM暴露的TWAS荟萃分析中，大多数参与者（约95%）被确定为波多黎各裔或黑人。长期PM与以下情况相关：）钙激活氯离子通道调节因子1（false discovery rate-adjusted [FDR-P] = 0.008）、联会复合体蛋白2（FDR-P = 0.01）和细胞色素p450家族2亚家族A成员6（FDR-P = 0.02）的表达上调；以及）外胚层发育不良蛋白A受体（FDR-P = 0.01）的表达下调。在一项荟萃分析中，钙激活氯离子通道调节因子1的上调与一种或多种阳性变应原特异性IgE（FDR-P < 0.00）、血液嗜酸性粒细胞增加（FDR-P < 0.001）和总IgE（FDR-P < 0.001）相关。在主要为波多黎各裔和黑人的哮喘青少年的TWAS荟萃分析中，长期PM暴露与气道上皮钙激活氯离子通道调节因子1的表达上调相关，进而与2型高免疫生物标志物相关。
