PURPOSE OF THE STUDY.
To compare the age-specific relationship between serum vitamin D (25-OH-D) levels and allergic sensitization, vitamin D receptor (VDR) activation pathways, peripheral blood mononuclear cell (PBMC) steroid responsiveness, and inhaled corticosteroid (ICS) requirements in children and adults with asthma.
One hundred three patients with asthma (53 children, 50 adults) and 102 healthy control subjects (51 children, 51 adults) were matched for age, gender, race, and BMI.
Serum 25-OH-D levels were checked during the winter in all subjects. Inducible markers of VDR activation (cytochrome P450 family 24 [cyp24a] mRNA and plasma cathelicidin [LL-37]) were measured. Tumor necrosis factor (TNF)-α and interleukin (IL)-13 were measured after in vitro stimulation of PBMC with dexamethasone.
Although there was great overlap in 25-OH-D levels between groups, asthmatics had a higher rate of vitamin D deficiency (<20 ng/mL) than healthy control subjects (56.8% vs 47.6%). The level of vitamin D–regulated targets (cyp24a and LL-37) correlated with 25-OH-D level in children, but only cyp24a had a similar correlation in adults. There was a significant inverse correlation between 25-OH-D and serum immunoglobulin (Ig) E in children but not adults. Dust mite–specific IgE was associated with lower 25-OH-D levels, but there was no such association in adults or to specific IgE levels for other aeroallergens. In children, but not adults, 25-OH-D levels had a significant inverse correlation with ICS requirement in the patients with asthma. A similar inverse correlation between 25-OH-D level and cyp24a and LL-37 was seen only in children. Cyp24a expression by PBMC correlated with the degree of TNF-α and IL-13 suppression by dexamethasone only in children. All of these associations were stronger in children aged 6 to 12 years than those aged 13 to 17 years. In the older children, the associations did not reach statistical significance.
There are significant associations between serum vitamin D level, inhaled corticosteroid requirement for asthma, and in vitro responsiveness to corticosteroids in children (particularly 6- to 12-year-olds) but not in adults.
There has been a surge of interest in vitamin D and its effects on numerous biological functions. Many associations are based on epidemiologic studies, including the role of vitamin D in atopic diseases. It is not clear if the rate of vitamin D deficiency and insufficiency has increased or if there is just greater awareness of the problem. This study demonstrates the association of 25-OH-D levels with biologic function, particularly in school-age children. Because the study was done in the winter, it is not clear if the same associations would be found in the summer when endogenous 25-OH-D levels are likely to be higher. It is also not clear why the associations were strongest in the youngest subjects. Finally, it is not clear if vitamin D supplementation would change the results or improve asthma outcomes in the study population. Nonetheless, this study suggests the opportunity for early intervention in young children with asthma. At the very least, it is another reason to recommend that children “turn off the screens” and go outside to play.
- Copyright © 2012 by the American Academy of Pediatrics