Association between vitamin D levels and psychological stress-induced asthma prevalence: an untargeted metabolomics study combined with the NHANES database

Background The incidence of psychological stress-induced asthma (PSA) is increasing annually, and numerous studies have shown that vitamin D is associated with the development of asthma, anxiety, and depression. However, to date, no studies have clarified the relationship between vitamin D levels and the prevalence of PSA. Therefore, this study aimed to integrate an analysis based on the National Health and Nutrition Examination Survey (NHANES) database with untargeted metabolomics to explore the potential association between vitamin D and PSA. Methods This study integrates a cross-sectional analysis based on the NHANES database with a prospective cohort study incorporating untargeted metabolomics. A total of 2165 adults with asthma and 2331 adults with PSA from the NHANES cycles (2007–2012 and 2015–2018) were included to evaluate the association between vitamin D levels and the incidence of PSA. Multivariable logistic regression, restricted cubic spline modeling, and subgroup analyses were performed. For external validation, 60 adults with asthma and PSA were recruited, and untargeted metabolomics was used to measure plasma calcidiol levels. The association between vitamin D levels and PSA was assessed using regression models. Results In the NHANES study, higher vitamin D levels were independently associated with a lower incidence of PSA (OR = 0.9967, p = 0.033). This association was particularly evident for depression-dominant PSA levels (OR = 0.9929, p 0.001) and exhibited a significant non-linear relationship ( p –non-linear = 0.04). When vitamin D levels were 67 nmol/L, the incidence of PSA (depression) increased significantly ( p = 0.02). Lower daily vitamin D intake was associated with significantly higher incidence rates of PSA and PSA (depression). In the Chinese cohort, higher calcidiol levels were potentially associated with a lower incidence of PSA (OR = 0.735, p = 0.0404), which warrants further validation in future studies. Sensitivity analyses confirmed the robustness of these findings with respect to PSA levels. Conclusion Our findings suggest that lower vitamin D status may be associated with a higher likelihood of PSA. Specifically, lower circulating vitamin D levels and lower daily vitamin D intake were associated with higher odds of PSA. These observations may provide a potential basis for future research on the clinical evaluation and management of PSA levels.