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Phthalate Exposure and Oxidative/Nitrosative Stress in Childhood Asthma: A Nested Case-Control Study with Propensity

Jung-Wei Chang1, Hsin-Chang Chen2, Heng-Zhao Hu1

  • 1Institute of Environmental and Occupational Health Sciences, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.

Biomedicines
|June 24, 2022
PubMed

Insights

Low-dose phthalate exposure, particularly monobenzyl phthalate (MBzP), is linked to childhood asthma. This study found phthalates may enhance immune responses, contributing to asthma development through oxidative stress and lipid peroxidation mechanisms.

Area of Science:

  • Environmental Health Sciences
  • Pediatric Allergy and Immunology
  • Toxicology

Background:

  • The link between low-dose phthalate exposure and childhood asthma remains unclear.
  • Phthalates are common endocrine disruptors found in indoor dust.
  • Potential mechanisms involve oxidative stress, nitrosative stress, and lipid peroxidation.

Purpose of the Study:

  • To investigate the association between low-dose phthalate exposure and childhood asthma.
  • To explore the mechanistic biomarkers related to oxidative/nitrosative stress and lipid peroxidation.
  • To determine the individual and mixed effects of phthalates on asthma development.

Main Methods:

  • A propensity score-matched case-control study design was employed (41 cases, 111 controls).
  • Urinary concentrations of phthalate metabolites were measured.
  • Five mechanistic biomarkers were assessed: 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2Gua), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), 8-isoprostaglandin F2α (8-isoPF2α), and malondialdehyde (MDA).

Main Results:

  • Significantly higher median monobenzyl phthalate (MBzP) concentrations were found in children with asthma.
  • High monomethyl phthalate (MMP) and mono-iso-butyl phthalate (MiBP) exposures were associated with specific biomarkers of oxidative stress (8-NO2Gua, 8-isoPF2α).
  • Weighted quantile sum regression indicated MBzP was the primary contributor to the observed associations.

Conclusions:

  • Low-dose phthalate exposure, especially MBzP, is associated with childhood asthma.
  • Phthalates may act as adjuvants, enhancing immune system responses implicated in asthma.
  • Findings highlight the role of phthalates in asthma pathogenesis via oxidative and lipid peroxidation pathways.

Keywords:
asthmaoxidative stressphthalatespropensity score matching

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