COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Research Unit for Environment, Work and Health, Department of Public Health, Aarhus University, Aarhus, Denmark.
EBioMedicine. 2023 Aug;94:104699. doi: 10.1016/j.ebiom.2023.104699. Epub 2023 Jul 8.
Exposure to perfluoroalkyl substances may affect offspring immune development and thereby increase risk of childhood asthma, but the underlying mechanisms and asthma phenotype affected by such exposure is unknown.
In the Danish COPSAC2010 cohort of 738 unselected pregnant women and their children plasma PFOS and PFOA concentrations were semi-quantified by untargeted metabolomics analyses and calibrated using a targeted pipeline in mothers (gestation week 24 and 1 week postpartum) and children (age ½, 1½ and 6 years). We examined associations between pregnancy and childhood PFOS and PFOA exposure and childhood infections, asthma, allergic sensitization, atopic dermatitis, and lung function measures, and studied potential mechanisms by integrating data on systemic low-grade inflammation (hs-CRP), functional immune responses, and epigenetics.
Higher maternal PFOS and PFOA exposure during pregnancy showed association with a non-atopic asthma phenotype by age 6, a protection against sensitization, and no association with atopic asthma or lung function, or atopic dermatitis. The effect was primarily driven by prenatal exposure. There was no association with infection proneness, low-grade inflammation, altered immune responses or epigenetic changes.
Prenatal exposure to PFOS and PFOA, but not childhood exposure, specifically increased the risk of low prevalent non-atopic asthma, whereas there was no effect on atopic asthma, lung function, or atopic dermatitis.
All funding received by COPSAC are listed on www.copsac.com. The Lundbeck Foundation (Grant no R16-A1694); The Novo Nordic Foundation (Grant nos NNF20OC0061029, NNF170C0025014, NNF180C0031764); The Ministry of Health (Grant no 903516); Danish Council for Strategic Research (Grant no 0603-00280B); and The Capital Region Research Foundation have provided core support to the COPSAC research center. COPSAC acknowledges the National Facility for Exposomics (SciLifeLab, Sweden) for supporting calibration of the untargeted metabolomics PFAS data. BC and AS has received funding for this project from the European Union's Horizon 2020 research and innovation programme (BC: grant agreement No. 946228 DEFEND; AS: grant agreement No. 864764 HEDIMED).
接触全氟烷基物质可能会影响后代的免疫发育，从而增加儿童哮喘的风险，但这种接触影响哮喘表型和潜在机制尚不清楚。
在丹麦 COPSAC2010 队列的 738 名未选择的孕妇及其儿童中，通过非靶向代谢组学分析半定量检测血浆 PFOS 和 PFOA 浓度，并使用针对母亲（妊娠 24 周和产后 1 周）和儿童（年龄半岁、1 岁半和 6 岁）的靶向分析进行校准。我们研究了妊娠和儿童时期 PFOS 和 PFOA 暴露与儿童感染、哮喘、过敏致敏、特应性皮炎和肺功能测量之间的关联，并通过整合系统低度炎症（hs-CRP）、功能免疫反应和表观遗传学数据来研究潜在机制。
母亲妊娠期间较高的 PFOS 和 PFOA 暴露与 6 岁时非特应性哮喘表型有关，与致敏呈保护作用，与特应性哮喘或肺功能或特应性皮炎无关。这种影响主要是由产前暴露引起的。与感染倾向、低度炎症、免疫反应改变或表观遗传改变无关。
PFOS 和 PFOA 的产前暴露，而不是儿童时期的暴露，特别是增加了低流行的非特应性哮喘的风险，而对特应性哮喘、肺功能或特应性皮炎没有影响。
COPSAC 获得的所有资金都列在 www.copsac.com 上。Lundbeck 基金会（赠款号 R16-A1694）；诺和诺德基金会（赠款号 NNF20OC0061029、NNF170C0025014、NNF180C0031764）；卫生部（赠款 903516）；丹麦战略研究理事会（赠款 0603-00280B）；和首都地区研究基金会为 COPSAC 研究中心提供了核心支持。COPSAC 感谢国家暴露组学设施（瑞典 SciLifeLab）支持校准非靶向代谢组学 PFAS 数据。BC 和 AS 已从欧盟地平线 2020 研究和创新计划获得该项目的资金（BC：赠款协议 No. 946228 DEFEND；AS：赠款协议 No. 864764 HEDIMED）。
