New study links perfluoroalkyl substance exposure to childhood asthma phenotypes

A recent study published in the eBioMedicine Journal evaluated the effects of exposure to perfluoroalkyl substances on asthma phenotypes.

survey: Exposure to perfluoroalkyl substances and asthma phenotypes in childhood: the COPSAC2010 cohort study. Image credit: RybalchenkoNadezhda/Shutterstock.com

Background

Atopic diseases and asthma are early immune diseases and represent a complex etiology. Environmental exposure to xenobiotics has increased in recent generations.

Perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) are the most studied per- and polyfluoroalkyl substances (PFAS). PFOS and PFOA detectable in maternal blood can cross the placental barrier and have been detected in cord blood and amniotic fluid.

Exposure to PFOA or PFOS has been studied in relation to childhood asthma. A recent meta-analysis showed increased risks of atopic dermatitis and allergic rhinitis due to PFOS and PFOA, respectively, but the associations with asthma were controversial.

However, asthma phenotypes (atopic and non-atopic) were not stratified, which is crucial given that childhood asthma is complex with heterogeneous diagnostic protocols.

About the research

In the current study, researchers examined the associations of pregnancy and early childhood exposure to PFOA and PFOS with asthma phenotypes. This was part of an ongoing prospective Copenhagen Study of Asthma in Childhood 2010 (COPSAC2010) mother-child cohort involving 738 women.

Pregnant subjects were invited to participate in 2008-10. Subjects and their children underwent 14 clinical and emergency visits during the first six years of life. Personal interviews were conducted at clinic visits by physicians and research assistants. Family, medical, socioeconomic, and environmental history 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 a targeted reanalysis and calibration channel.

Primary study outcomes included asthma and allergies; secondary outcomes were early-life infections and measures of lung function.

Covariates included were a priori factors associated with PFOA or PFOS, such as parity, race, prepregnancy body mass index (BMI), maternal age and asthma, urban environment, presence of PFOS or PFOA in the water supply, and social circumstances. DNA methylation was assessed in the nasal epithelium at six years of age.

Spearman’s correlation coefficient was used to assess the correlations of PFOA and PFOS. A principal component analysis (PCA) was performed to assess the covariance of PFOA and PFOS. The effects of PFOA or PFOS exposure were examined separately. Cox, logistic, and linear regression models analyzed time-to-event, binary, and continuous outcomes.

Findings

Valid measurements of PFOS and PFOA were available for 727 and 684 women at 24 weeks’ gestation and one week postpartum, respectively. Similarly, 602, 606, and 513 children had valid measures at six months, 18 months, and six years, respectively.

Maternal concentrations of PFOS and PFOA were highly correlated; child concentrations in early life are also related within child and between mother and child.

PCA revealed that PFOA and PFOS were highly correlated. At six years, 437 children had evidence of asthma, inhalant sensitization and eosinophils. Non-atopic asthma was observed in 16 children and atopic asthma in 24 children. Maternal concentrations of PFOA and PFOS are associated with asthma at six years, driven by the association with nonatopic phenotypes.

Childhood PFOA and PFOS levels 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 early childhood infections. PFOS or PFOA were not associated with lung spirometry measurements at six years.

A statistically significant association was observed between maternal PFOA levels and high-sensitivity C-reactive protein concentrations at 24 weeks’ gestation.

Low concentrations of PFOA or PFOS are associated with an innate immune response to bacterial or viral ligands and T-cell stimulations. PFOA or PFOS levels during pregnancy and childhood were not associated with changes in DNA methylation in the nasal epithelium at six years.

Conclusions

The findings showed that higher prenatal exposure to PFOS and PFOA was associated with an increased risk of a nonatopic asthma phenotype up to six years. No associations were reported for asthma exacerbations, atopic asthma, lung function, atopic dermatitis and frequent infections.

In parallel, prenatal PFOS was associated with a lower risk of sensitization to inhalant allergens. The study revealed an association between maternal exposure and a higher risk of a nonatopic asthma phenotype at six years, pointing to potential asthma subtype-specific prenatal programming.