Early-life oxidative stress as a driver of childhood asthma: mechanisms and epidemiologic evidence
TL;DR
Current mechanistic and epidemiologic evidence suggests that oxidative stress may represent an important biological pathway linking early-life environmental exposures with asthma susceptibility, although further studies are needed to clarify its role within the complex network of factors contributing to asthma development.
Abstract
Early-life oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) and reactive nitrogen species (RNS) and antioxidant defenses, has increasingly been proposed as an important contributor to the developmental origins of childhood asthma. Prenatal and early postnatal exposures—including pollutants, tobacco smoke, maternal distress, nutritional imbalance, and allergen-derived oxidase activity—may disrupt epithelial integrity and redox-regulated immune pathways, potentially predisposing the developing lung to allergic inflammation. To synthesize current mechanistic and epidemiologic evidence on how oxidative stress during early life may contribute to asthma development, with particular focus on environmental drivers, redox–immune interactions, and gene-environment susceptibility. A structured review of PubMed, Scopus, and Embase identified peer-reviewed English-language studies from birth cohorts, mechanistic models, and biomarker analyses evaluating oxidative stress, antioxidant capacity, and asthma-related outcomes. Environmental oxidants and nutritional deficiencies may increase ROS production, promoting epithelial injury, activation of redox-sensitive pathways such as NF-κB and MAPK, and the release of epithelial alarmins including IL-33, IL-25, and thymic stromal lymphopoietin (TSLP). These signals can influence innate immune activation and antigen-presenting cell function, favoring Th2/Th17-biased immune responses. Genetic variants in antioxidant pathways, including GSTM1, GSTP1, and Nrf2, may further modify susceptibility to oxidant exposures. Epidemiologic studies from birth cohorts report associations between early-life oxidative exposures, reduced lung growth, wheezing, allergic sensitization, and asthma risk. Current mechanistic and epidemiologic evidence suggests that oxidative stress may represent an important biological pathway linking early-life environmental exposures with asthma susceptibility, although further studies are needed to clarify its role within the complex network of factors contributing to asthma development.