TY - JOUR
T1 - Associations between repeated measures of urinary phthalate metabolites and biomarkers of oxidative stress in a rural agricultural cohort of children with asthma
AU - Babadi, Ryan S.
AU - Riederer, Anne M.
AU - Sampson, Paul D.
AU - Sathyanarayana, Sheela
AU - Kavanagh, Terrance J.
AU - Krenz, Jennifer E.
AU - Andra, Syam S.
AU - Kim-Schulze, Seunghee
AU - Jansen, Karen L.
AU - Torres, Elizabeth
AU - Perez, Adriana
AU - Younglove, Lisa R.
AU - Tchong-French, Maria I.
AU - Karr, Catherine J.
N1 - Funding Information:
Research on urinary phthalate metabolites, creatinine, and biomarkers of oxidative stress reported in this publication was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number U2CES026561 . The Mount Sinai CHEAR/HHEAR laboratory hub acknowledges Anil Meher, Divya Pulivarthi, Srinivasan Narasimhan, and Shirisha Yelamanchili who performed the measurements of phthalates metabolites and creatinine in urine. This work was supported in part by funding from NIH / NIEHS : U2C ES026561 and P30 ES023515 . The content on concentrations of urinary phthalate metabolites, creatinine, and biomarkers of oxidative stress is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We wish to thank the Human Immune Monitoring Center at the Icahn School of Medicine at Mount Sinai for their laboratory analysis and support accessed through the NIEHS Children's Health Exposure Analysis Resource (CHEAR) program, as well as the Human Health Exposure Analysis Resource (HHEAR), and corresponding Data Centers. We thank Lincoln Diagnostics for donation of skin prick testing materials. Graphical abstract generated in part with R packages "ggplot2", "usmap", and "maps". This research would not have been possible without the participating children and their households, as well as the HAPI field team.
Funding Information:
Design of the study and collection, analysis, and interpretation of data and writing of the manuscript was supported by (i) funders of the Home Air in Agriculture Pediatric Intervention (HAPI) trial ( National Institute of Environmental Health Sciences (NIEHS) Research to Action Program (NIEHS 5R01ES023510 ) and the University of Washington (UW) Interdisciplinary Center for Exposures, Diseases, Genomics and the Environment (NIEHS P30ES007033 )), and (ii) the UW NIEHS-sponsored Biostatistics, Epidemiologic and Bioinformatic Training in Environmental Health (BEBTEH) Training Grant (NIEHS T32ES015459 ).
Funding Information:
Design of the study and collection, analysis, and interpretation of data and writing of the manuscript was supported by (i) funders of the Home Air in Agriculture Pediatric Intervention (HAPI) trial (National Institute of Environmental Health Sciences (NIEHS) Research to Action Program (NIEHS 5R01ES023510) and the University of Washington (UW) Interdisciplinary Center for Exposures, Diseases, Genomics and the Environment (NIEHS P30ES007033)), and (ii) the UW NIEHS-sponsored Biostatistics, Epidemiologic and Bioinformatic Training in Environmental Health (BEBTEH) Training Grant (NIEHS T32ES015459).Research on urinary phthalate metabolites, creatinine, and biomarkers of oxidative stress reported in this publication was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number U2CES026561. The Mount Sinai CHEAR/HHEAR laboratory hub acknowledges Anil Meher, Divya Pulivarthi, Srinivasan Narasimhan, and Shirisha Yelamanchili who performed the measurements of phthalates metabolites and creatinine in urine. This work was supported in part by funding from NIH/NIEHS: U2C ES026561 and P30 ES023515. The content on concentrations of urinary phthalate metabolites, creatinine, and biomarkers of oxidative stress is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We wish to thank the Human Immune Monitoring Center at the Icahn School of Medicine at Mount Sinai for their laboratory analysis and support accessed through the NIEHS Children's Health Exposure Analysis Resource (CHEAR) program, as well as the Human Health Exposure Analysis Resource (HHEAR), and corresponding Data Centers. We thank Lincoln Diagnostics for donation of skin prick testing materials. Graphical abstract generated in part with R packages "ggplot2", "usmap", and "maps". This research would not have been possible without the participating children and their households, as well as the HAPI field team.
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/11/20
Y1 - 2022/11/20
N2 - Phthalate exposure is widespread, and studies suggest an adverse relationship with asthma morbidity, including some support for oxidative stress as an underlying pathophysiological mechanism. Urinary phthalate metabolites have been associated with biomarkers of oxidative stress, but data are few in children diagnosed with asthma. We used participant data from the Home Air in Agriculture Pediatric Intervention Trial (HAPI) to examine longitudinal relationships between phthalates and oxidative stress in a cohort of Latino children with asthma residing in an agricultural community. We used linear mixed-effects models to estimate associations between 11 urinary phthalate metabolites (and one summed measure of di-2-ethylhexyl phthalate (DEHP) metabolites, ∑DEHP) and two urinary biomarkers of oxidative stress: a biomarker of lipid peroxidation via measure of 8-isoprostane and a biomarker of DNA/RNA oxidative damage via combined measure of 8-hydroxydeoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-OHG), and 8-hydroxyguanine. Seventy-nine participants provided 281 observations. In covariate-adjusted models, we observed significant positive relationships between all phthalate metabolites and 8-isoprostane, effect sizes ranging from a 9.3 % (95 % CI: 4.2 %–14.7 %) increase in 8-isoprostane for each 100 % increase (i.e., doubling) of mono-(carboxy-isooctyl) phthalate (MCIOP), to a 21.0 % (95 % CI: 14.3 %–28.2 %) increase in 8-isoprostane for each doubling of mono-n-butyl phthalate (MNBP). For each doubling of mono-(carboxy-isononyl) phthalate (MCINP) and mono-ethyl phthalate (MEP), the DNA/RNA oxidative damage biomarker increased by 6.0 % (95 % CI: 0.2 %–12.2 %) and 6.5 % (95 % CI: 1.4 %–11.9 %), respectively. In conclusion, we provide unique data suggesting phthalate exposure is positively associated with oxidative stress in children with asthma. Our repeat measures provide novel identification of a consistent effect of phthalates on oxidative stress in children with asthma via lipid peroxidation. Confirmation in future studies of children with asthma is needed to enhance understanding of the role of phthalates in childhood asthma morbidity.
AB - Phthalate exposure is widespread, and studies suggest an adverse relationship with asthma morbidity, including some support for oxidative stress as an underlying pathophysiological mechanism. Urinary phthalate metabolites have been associated with biomarkers of oxidative stress, but data are few in children diagnosed with asthma. We used participant data from the Home Air in Agriculture Pediatric Intervention Trial (HAPI) to examine longitudinal relationships between phthalates and oxidative stress in a cohort of Latino children with asthma residing in an agricultural community. We used linear mixed-effects models to estimate associations between 11 urinary phthalate metabolites (and one summed measure of di-2-ethylhexyl phthalate (DEHP) metabolites, ∑DEHP) and two urinary biomarkers of oxidative stress: a biomarker of lipid peroxidation via measure of 8-isoprostane and a biomarker of DNA/RNA oxidative damage via combined measure of 8-hydroxydeoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-OHG), and 8-hydroxyguanine. Seventy-nine participants provided 281 observations. In covariate-adjusted models, we observed significant positive relationships between all phthalate metabolites and 8-isoprostane, effect sizes ranging from a 9.3 % (95 % CI: 4.2 %–14.7 %) increase in 8-isoprostane for each 100 % increase (i.e., doubling) of mono-(carboxy-isooctyl) phthalate (MCIOP), to a 21.0 % (95 % CI: 14.3 %–28.2 %) increase in 8-isoprostane for each doubling of mono-n-butyl phthalate (MNBP). For each doubling of mono-(carboxy-isononyl) phthalate (MCINP) and mono-ethyl phthalate (MEP), the DNA/RNA oxidative damage biomarker increased by 6.0 % (95 % CI: 0.2 %–12.2 %) and 6.5 % (95 % CI: 1.4 %–11.9 %), respectively. In conclusion, we provide unique data suggesting phthalate exposure is positively associated with oxidative stress in children with asthma. Our repeat measures provide novel identification of a consistent effect of phthalates on oxidative stress in children with asthma via lipid peroxidation. Confirmation in future studies of children with asthma is needed to enhance understanding of the role of phthalates in childhood asthma morbidity.
KW - Asthma
KW - Children
KW - DNA/RNA damage
KW - Lipid peroxidation
KW - Oxidative stress
KW - Phthalate exposure
UR - http://www.scopus.com/inward/record.url?scp=85135804225&partnerID=8YFLogxK
U2 - 10.1016/j.scitotenv.2022.157493
DO - 10.1016/j.scitotenv.2022.157493
M3 - Article
C2 - 35878846
AN - SCOPUS:85135804225
SN - 0048-9697
VL - 848
JO - Science of the Total Environment
JF - Science of the Total Environment
M1 - 157493
ER -