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Ambient air pollution exposure and influenza virus infection have been documented to be independently associated with reduced lung function previously. Influenza vaccination plays an important role in protecting against influenza-induced severe diseases. However, no study to date has focused on whether influenza vaccination may modify the associations between ambient air pollution exposure and lung function. We undertook a cross-sectional study of 6740 children aged 7–14 years into Seven Northeast Cities (SNEC) Study in China during 2012–2013. We collected information from parents/guardians about sociodemographic factors and influenza vaccination status in the past three years. Lung function was measured using portable electronic spirometers. Machine learning methods were used to predict 4-year average ambient air pollutant exposures to nitrogen dioxide (NO 2) and particulate matter with an aerodynamic diameter <1 μm (PM 1), <2.5 μm (PM 2.5) and <10 μm (PM 10). Two-level linear and logistic regression models were used to assess interactions between influenza vaccination and long-term ambient air pollutants exposure on lung function reduction, controlling for potential confounding factors. Ambient air pollution were observed significantly associated with reductions in lung function among children. We found significant interactions between influenza vaccination and air pollutants on lung function, suggesting greater vulnerability to air pollution among unvaccinated children. For example, an interaction (p interaction = 0.002) indicated a −283.44 mL (95% CI: −327.04, −239.83) reduction in forced vital capacity (FVC) per interquartile range (IQR) increase in PM 1 concentrations among unvaccinated children, compared with the −108.24 mL (95%CI: −174.88, −41.60) reduction in FVC observed among vaccinated children. Results from logistic regression models also showed stronger associations between per IQR increase in PM 1 and lung function reduction measured by FVC and peak expiratory flow (PEF) among unvaccinated children than the according ORs among vaccinated children [i.e., Odds Ratio (OR) for PM 1 and impaired FVC: 2.33 (95%CI: 1.79, 3.03) vs 1.65 (95%CI: 1.20, 2.28); OR for PM 2.5 and impaired PEF: 1.45 (95%CI: 1.12,1.87) vs 1.04 (95%CI: 0.76,1.43)]. The heterogeneity of the modification by influenza vaccination of the associations between air pollution exposure and lung function reduction appeared to be more substantial in girls than in boys. Our results suggest that influenza vaccination may moderate the detrimental effects of ambient air pollution on lung function among children. This study provides new insights into the possible co-benefits of strengthening and promoting global influenza vaccination programs among children. Image 1 • No study on interactions between flu vaccine and air pollution on lung function. • Flu vaccine may mitigate the detrimental effects of air pollution on lung function. • The interactions appeared to be more substantial in girls than in boys. [ABSTRACT FROM AUTHOR]