Exposures to perfluoroalkyl substances and asthma phenotypes in childhood: an investigation of the COPSAC2010 cohort

Astrid Sevelsted; Casper-Emil Tingskov Pedersen; Gözde Gürdeniz; Morten Arendt Rasmussen; Jörg Schullehner; Kalliroi Sdougkou; Jonathan W Martin; Jessica Lasky-Su; Andreanne Morin; Carole Ober; Ann-Marie Malby Schoos; Jakob Stokholm; Klaus Bønnelykke; Bo L. Chawes; Hans Bisgaard

doi:10.1016/j.ebiom.2023.104699

Exposures to perfluoroalkyl substances and asthma phenotypes in childhood: an investigation of the COPSAC2010 cohort

Astrid Sevelsted
, Casper-Emil Tingskov Pedersen
, Gözde Gürdeniz
, Morten Arendt Rasmussen
, Jörg Schullehner
, Kalliroi Sdougkou
, Jonathan W Martin
, Jessica Lasky-Su
, Andreanne Morin
, Carole Ober
, Ann-Marie Malby Schoos
, Jakob Stokholm
, Klaus Bønnelykke
, Bo L. Chawes^*
, Hans Bisgaard

^*Corresponding author for this work

Paediatrics (NSR)

Research output: Contribution to journal › Article › Research › peer-review

Abstract

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).

Original language	English
Article number	104699
Pages (from-to)	104699
Number of pages	12
Journal	EBioMedicine
Volume	94
Early online date	8 Jul 2023
DOIs	https://doi.org/10.1016/j.ebiom.2023.104699
Publication status	Published - Aug 2023

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 & nbsp;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).

Funders	Funder number
Lundbeck Foundation	R16-A1694
Novo Nordisk Foundation	NNF20OC0061029, NNF170C0025014, NNF180C0031764
Ministry of Health	903516
Danish Council for Strategic Research	0603-00280B
European Union	946228 DEFEND, 864764 HEDIMED

Keywords

Asthma/etiology
Dermatitis, Atopic
Female
Fluorocarbons/toxicity
Humans
Inflammation/complications
Mothers
Phenotype
Pregnancy
Prenatal Exposure Delayed Effects

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10.1016/j.ebiom.2023.104699

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Sevelsted, A., Pedersen, C.-E. T., Gürdeniz, G., Rasmussen, M. A., Schullehner, J., Sdougkou, K., Martin, J. W., Lasky-Su, J., Morin, A., Ober, C., Schoos, A.-M. M., Stokholm, J., Bønnelykke, K., Chawes, B. L., & Bisgaard, H. (2023). Exposures to perfluoroalkyl substances and asthma phenotypes in childhood: an investigation of the COPSAC2010 cohort. EBioMedicine, 94, 104699. Article 104699. https://doi.org/10.1016/j.ebiom.2023.104699

@article{11cbd15497904a319aefb66ab6749965,

title = "Exposures to perfluoroalkyl substances and asthma phenotypes in childhood: an investigation of the COPSAC2010 cohort",

abstract = "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).",

keywords = "Asthma/etiology, Dermatitis, Atopic, Female, Fluorocarbons/toxicity, Humans, Inflammation/complications, Mothers, Phenotype, Pregnancy, Prenatal Exposure Delayed Effects",

author = "Astrid Sevelsted and Pedersen, \{Casper-Emil Tingskov\} and G{\"o}zde G{\"u}rdeniz and Rasmussen, \{Morten Arendt\} and J{\"o}rg Schullehner and Kalliroi Sdougkou and Martin, \{Jonathan W\} and Jessica Lasky-Su and Andreanne Morin and Carole Ober and Schoos, \{Ann-Marie Malby\} and Jakob Stokholm and Klaus B{\o}nnelykke and Chawes, \{Bo L.\} and Hans Bisgaard",

year = "2023",

month = aug,

doi = "10.1016/j.ebiom.2023.104699",

language = "English",

volume = "94",

pages = "104699",

journal = "EBioMedicine",

issn = "2352-3964",

publisher = "Elsevier B.V.",

}

Sevelsted, A, Pedersen, C-ET, Gürdeniz, G, Rasmussen, MA, Schullehner, J, Sdougkou, K, Martin, JW, Lasky-Su, J, Morin, A, Ober, C, Schoos, A-MM , Stokholm, J, Bønnelykke, K, Chawes, BL & Bisgaard, H 2023, 'Exposures to perfluoroalkyl substances and asthma phenotypes in childhood: an investigation of the COPSAC2010 cohort', EBioMedicine, vol. 94, 104699, pp. 104699. https://doi.org/10.1016/j.ebiom.2023.104699

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 L.

AU - Bisgaard, Hans

PY - 2023/8

Y1 - 2023/8

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 - Asthma/etiology

KW - Dermatitis, Atopic

KW - Female

KW - Fluorocarbons/toxicity

KW - Humans

KW - Inflammation/complications

KW - Mothers

KW - Phenotype

KW - Pregnancy

KW - Prenatal Exposure Delayed Effects

U2 - 10.1016/j.ebiom.2023.104699

DO - 10.1016/j.ebiom.2023.104699

M3 - Article

C2 - 37429082

SN - 2352-3964

VL - 94

SP - 104699

JO - EBioMedicine

JF - EBioMedicine

M1 - 104699

ER -

Exposures to perfluoroalkyl substances and asthma phenotypes in childhood: an investigation of the COPSAC2010 cohort

Abstract

Funding

Keywords

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