A recent study published in the eBioMedicine Journal evaluated the effects of exposure to perfluoroalkyl substances on asthma phenotypes.
Study: Exposures to perfluoroalkyl substances and asthma phenotypes in childhood: an investigation of the COPSAC2010 cohort. Image Credit: RybalchenkoNadezhda/Shutterstock.com
Atopic diseases and asthma are early immune diseases and present complex etiologies. Environmental exposure to xenobiotics has increased in recent generations.
Perfluorooctanoate (PFOA) and perfluoro octane sulfonate (PFOS) are the most studied per-and poly-fluoroalkyl substances (PFAS). PFOS and PFOA, detectable in maternal blood, can cross the placental barrier and have been detected in cord blood and amniotic fluid.
PFOA or PFOS exposure has been studied regarding childhood asthma. Recently, a meta-analysis showed increased risks of atopic dermatitis and allergic rhinitis due to PFOS and PFOA, respectively, but associations with asthma were inconsistent.
However, asthma phenotypes (atopic and non-atopic) were not stratified, which is crucial given that childhood asthma is complex with heterogeneous diagnosis protocols.
About the study
In the present study, researchers explored the associations of pregnancy and early childhood exposure to PFOA and PFOS with asthma phenotypes. This was part of an ongoing Copenhagen prospective study of asthma in childhood 2010 (COPSAC2010) mother-child cohort, comprising 738 females.
Pregnant individuals were invited to participate during 2008-10. Subjects and their children completed 14 clinical and acute care visits in the first six years of life. Personal interviews were conducted at clinical visits by doctors and research assistants. Familial, medical, socio-economic, and environmental histories were assessed.
Using untargeted plasma metabolomics, the relative abundance of PFOA and PFOS was measured in blood samples of pregnant individuals at gestational weeks 24 and one week postpartum and children at six months, 18 months, and six years. Subsequently, 48 samples were quantified for PFOA and PFOS levels using targeted re-analysis and calibration pipeline.
The study’s primary outcomes included asthma and allergies; secondary outcomes were infections in early life and lung function measures.
Included covariates were a priori factors associated with PFOA or PFOS, such as parity, race, pre-pregnancy body mass index (BMI), maternal age and asthma, urbanicity, ever presence of PFOS or PFOA in water supply, and social circumstances. DNA methylation was evaluated in the nasal epithelium at six years.
Spearman’s correlation coefficient was used to estimate PFOA and PFOS correlations. Principal component analysis (PCA) was performed to assess the covariance of PFOA and PFOS. Effects of PFOA or PFOS exposure were separately investigated. Cox, logistic, and linear regression models analyzed time-to-event, binary, and continuous outcomes.
Valid PFOS and PFOA measurements were available for 727 and 684 females at gestational week 24 and one week postpartum, respectively. Similarly, 602, 606, and 513 children had valid measures at six months, 18 months, and six years, respectively.
Maternal PFOS and PFOA concentrations were highly correlated; child concentrations in early life were also correlated within the child and between mother and child.
PCA revealed that PFOA and PFOS were highly correlated. At six years, 437 children had data on asthma, inhalant sensitization, and eosinophils. Non-atopic asthma was observed in 16 children, and atopic asthma in 24 children. Maternal PFOA and PFOS concentrations were associated with asthma at six years, driven by the association with non-atopic phenotypes.
Childhood levels of PFOA and PFOS at six and 18 months were associated with a reduced risk of inhalant sensitization at six years. Childhood concentrations were not associated with asthma or atopic dermatitis.
Maternal and child concentrations of PFOA or PFOS were not associated with a higher risk of infections in early life. PFOS or PFOA were not associated with lung spirometry measures at six years.
A statistically significant association was observed between maternal PFOA levels and high-sensitivity C-reactive protein concentrations at gestational week 24.
Weak PFOA or PFOS concentrations were associated with innate immune responsiveness to bacterial or viral ligands and T-cell stimulations. Pregnancy and child levels of PFOA or PFOS were not related to changes in DNA methylation in the nasal epithelium at six years.
The findings showed that higher prenatal exposure to PFOS and PFOA was associated with an elevated risk of non-atopic asthma phenotype by six years. No associations were reported for asthma exacerbations, atopic asthma, lung function, atopic dermatitis, and common infections.
In parallel, prenatal PFOS was associated with a lower risk of inhalant allergen sensitization. The study revealed an association between maternal exposure and a higher risk of non-atopic asthma phenotype at six years, pointing towards potential asthma subtype-specific prenatal programming.
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. & Bisgaard, H. (2023) Exposures to perfluoroalkyl substances and asthma phenotypes in childhood: an investigation of the COPSAC2010 cohort. eBioMedicine, 94, p.104699. doi: 10.1016/j.ebiom.2023.104699. https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00264-5/fulltext