TY - JOUR

T1 - Exposures to perfluoroalkyl substances and asthma phenotypes in childhood

T2 - an investigation of the COPSAC2010 cohort

AU - Sevelsted, Astrid

AU - Pedersen, Casper Emil Tingskov

AU - Gürdeniz, Gözde

AU - Rasmussen, Morten Arendt

AU - Schullehner, Jörg

AU - Sdougkou, Kalliroi

AU - Martin, Jonathan W.

AU - Lasky-Su, Jessica

AU - Morin, Andreanne

AU - Ober, Carole

AU - Schoos, Ann Marie Malby

AU - Stokholm, Jakob

AU - Bønnelykke, Klaus

AU - Chawes, Bo

AU - Bisgaard, Hans

N1 - Publisher Copyright: © 2023 The Author(s)

PY - 2023

Y1 - 2023

N2 - Background: 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. Methods: 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. Findings: 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. Interpretations: 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. Funding: 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).

AB - Background: 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. Methods: 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. Findings: 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. Interpretations: 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. Funding: 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).

KW - Allergy

KW - Asthma

KW - Child

KW - FeNO

KW - hs-CRP

KW - MeSH

KW - Metabolomics

KW - Mother-child cohort

KW - PFOA

KW - PFOS

KW - Sensitization

KW - Xenobiotics

U2 - 10.1016/j.ebiom.2023.104699

DO - 10.1016/j.ebiom.2023.104699

M3 - Journal article

C2 - 37429082

AN - SCOPUS:85164266438

VL - 94

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

M1 - 104699

ER -