Passive Tobacco Smoke Exposure, Oxidative Stress and Pediatric Allergic and Obstructive Respiratory Diseases: A Systematic Review and a “Second Oxidative Hit” Hypothesis

Pediatric allergic and obstructive respiratory diseases are a leading cause of chronic childhood morbidity. Passive tobacco smoke exposure (TSE) is one of the most prevalent and preventable indoor pollutants affecting children, while oxidative stress is increasingly recognized as a key mechanism linking tobacco smoke exposure to airway inflammation. This systematic review critically evaluated the evidence connecting passive TSE to oxidative stress pathways in pediatric airway disease and integrated it into a "second oxidative hit" hypothesis. Following PRISMA 2020 guidelines, PubMed and MEDLINE were searched to identify studies assessing passive TSE, oxidative or antioxidant biomarkers, and respiratory outcomes in children. Of the 77 records identified, four studies met the inclusion criteria. Across the available evidence, passive TSE was associated with increased lipid peroxidation, NOX2 activation, oxidative-inflammatory signaling, depletion of antioxidant defenses, oxidative DNA damage, and impairment of redox-sensitive corticosteroid-response pathways, although findings were not uniform across studies. Clinically, passive TSE children showed persistent allergic rhinitis, greater wheezing severity, poorer asthma control and reduced corticosteroid responsiveness. Despite limited and heterogeneous evidence, the findings provide a biological rationale for a testable "second oxidative hit" hypothesis, whereby passive TSE, combined with a pre-existing inflammatory environment in the airways associated with the underlying disease, could produce an additional oxidative burden. Further prospective studies integrating standardized oxidative biomarkers and objective exposure assessment are needed to validate this hypothesis, and establish temporal and causal relationships, potentially supporting more targeted preventive and personalized strategies.