Mechanisms of Airway Inflammatory Diseases Under Ozone Single Exposure, Coexposure, and Triple Exposure With PM 2.5 and Heat: A Review

Climate change and air pollution are increasingly intertwined environmental challenges to airway health. Surface ozone, a major secondary pollutant, exerts adverse respiratory effects that are frequently exacerbated by coexposure to fine particulate matter (PM 2.5 ) or heat. This review summarizes evidence on the mechanisms linking ozone and typical ozone‐related coexposure and triple exposure to airway inflammatory diseases. Ozone initiates airway injury through oxidative reactions at the epithelial surface, leading to antioxidant imbalance, epithelial barrier dysfunction, NF‐κB/MAPK/NLRP3 activation, microbial dysbiosis, and neurogenic inflammation. Coexposure with PM 2.5 or heat may further amplify ozone toxicity through distinct but interconnected pathways. Ozone–PM 2.5 coexposure elicits additive or synergistic oxidative burden, whereby PM 2.5 acts as a chemical amplifier. In contrast, under ozone–heat coexposure, heat functions primarily as a biological sensitizer through heat stress responses, transient receptor potential (TRP)–mediated neuroimmune activation, and microbiota–metabolism perturbations. The immune–neuro–microbiota network may provide an integrative framework to explain how coexposures maintain persistent airway inflammation, whereas host factors such as pollen allergy determine the injury threshold and recovery capacity of organisms. The potential health effects of concurrent exposure to ozone, PM 2.5 , and heat remain largely unexplored. Triple exposure can overwhelm host compensatory systems via three interrelated mechanisms: increasing biologically effective exposure doses, reducing host tolerance, and converging upon shared defensive signaling cascades. This interplay elicits emergent health effects that cannot be inferred from single or pairwise exposure scenarios. Future studies should combine environmentally relevant chronic low‐dose coexposure models, multiomics approaches, and longitudinal population studies to identify susceptibility profiles, clarify interactive toxicological mechanisms, and improve risk assessment and targeted prevention strategies under the combined pressures of air pollution and climate change.