Associations between vitamin D status and biomarkers linked with inflammation in patients with asthma: a systematic review and meta-analysis of interventional and observational studies.

BACKGROUND: Numerous studies indicate an association between vitamin D status and inflammatory biomarkers in patients with asthma, but findings are inconsistent. This review aims to summarize the relationship between serum vitamin D status, assessed by 25-hydroxyvitamin D (25(OH)D) level, and inflammatory biomarkers in children and adults with asthma. METHODS: A literature search of interventional and observational studies on 25(OH)D up to November 2022 was conducted across six electronic databases. Outcomes of interest included a range of inflammatory biomarkers classified in four categories: T helper 2 (Th2) pro-inflammatory, non-Th2 pro-inflammatory, anti-inflammatory, and non-specific biomarkers. Study characteristics were extracted and risk of bias was evaluated using the American Academy of Nutrition and Dietetics tool. Meta-analysis was conducted on studies with a low risk of bias, while narrative reporting was used to present the direction of associations (positive, no association, or negative) for each biomarker, overall and within the low-risk studies. RESULTS: We included 71 studies (3 interventional, 68 observational) involving asthma patients. These studies investigated the association between serum 25(OH)D and Th2 pro-inflammatory biomarkers (N = 58), non-Th2 pro-inflammatory biomarkers (N = 18), anti-inflammatory biomarkers (N = 16), and non-specific biomarkers (N = 10). Thirteen (18.3%) studies, 50 (70.4%), and 8 (11.3%) were at high, moderate, and low risk of bias, respectively. In all studies, irrespective of risk of bias, the most frequently reported finding was no significant association, followed by a negative association between 25(OH)D and pro-inflammatory biomarkers and a positive association with anti-inflammatory biomarkers. In low-risk studies, one biomarker could be meta-analysed. The pooled estimate for 25(OH)D and serum IgE showed a negative association (β (95% CI)= - 0.33 (-0.65 to - 0.01); I = 88%; N = 4 studies). A negative association between 25(OH)D and blood eosinophils was also observed in the largest of three studies, as well as with cathelicidin (LL-37) in the only study reporting it. For other biomarkers, most low-risk studies revealed no significant association with 25(OH)D. CONCLUSION: Serum 25(OH)D is negatively associated with serum IgE and possibly with blood eosinophils and LL-37, supporting an in vivo immunomodulatory effect of 25(OH)D. Future research should employ rigorous methodologies and standardized reporting for meta-analysis aggregation to further elucidate these associations.