Decreased serum vitamin D levels in children with asthma are associated with increased corticosteroid use

Abstract

Background: There is little knowledge about clinical variables associated with vitamin D (VitD) insufficiency in asthmatic children.

Objective: We sought to investigate disease variables associated with VitD insufficiency in patients with childhood asthma and interaction of VitD with corticosteroid-mediated anti-inflammatory responses.

Methods: We analyzed 25-hydroxyvitamin D serum levels in 100 asthmatic children to investigate relationships between 25-hydroxyvitamin D levels and patients' characteristics. We determined VitD's effects on dexamethasone (DEX) induction of mitogen-activated protein kinase phosphatase 1 and IL-10 in PBMCs.

Results: The median 25-hydroxyvitamin D serum level was 31 ng/mL. Forty-seven percent of subjects had VitD levels in the insufficient range (<30 ng/mL), whereas 17% were VitD deficient (<20 ng/mL). Log(10) IgE (P = .01, rho = -0.25) and the number of positive aeroallergen skin prick test responses (P = .02, rho = -0.23) showed a significant inverse correlation with VitD levels, whereas FEV(1) percent predicted (P = .004, rho = 0.34) and FEV(1)/forced vital capacity ratio (P = .01, rho = 0.30) showed a significant positive correlation with VitD levels. The use of inhaled steroids (P = .0475), use of oral steroids (P = .02), and total steroid dose (P = .001) all showed significant inverse correlations with VitD levels. The amount of mitogen-activated protein kinase phosphatase 1 and IL10 mRNA induced by VitD plus DEX was significantly greater than that induced by DEX alone (P < .01). In an experimental model of steroid resistance in which DEX alone did not inhibit T-cell proliferation, addition of VitD to DEX resulted in significant dose-dependent suppression of cell proliferation.

Conclusions: Corticosteroid use and worsening airflow limitation are associated with lower VitD serum levels in asthmatic patients. VitD enhances glucocorticoid action in PBMCs from asthmatic patients and enhances the immunosuppressive function of DEX in vitro.

Figure 1

Distribution of vitD Levels. Vitamin D levels are expressed as serum 25-hydroxyvitamin D. The median value was 31 ng/mL. Forty-seven per cent of asthmatics had insufficient levels of vitD (less than 30 ng/mL).

Figure 2

Vitamin D (vitD) potentiated DEX-mediated transactivation in human PBMC: enhances DEX induction of MKP-1 (A) and IL-10 (B) mRNA. PBMC from patients with asthma were cultured with 10nM vitD or media alone for 24h and supplemented with 10 or 100 nM of DEX for the last 3h of culture. MKP-1 mRNA levels were detected by Real-Time PCR, and were normalized to actin mRNA. Values represent mean±SEM (n=11).

Figure 2

Vitamin D (vitD) potentiated DEX-mediated transactivation in human PBMC: enhances DEX induction of MKP-1 (A) and IL-10 (B) mRNA. PBMC from patients with asthma were cultured with 10nM vitD or media alone for 24h and supplemented with 10 or 100 nM of DEX for the last 3h of culture. MKP-1 mRNA levels were detected by Real-Time PCR, and were normalized to actin mRNA. Values represent mean±SEM (n=11).

Figure 3

Vitamin D augments DEX effect on TSST-1 stimulated lymphocyte proliferation in human PBMC. PBMC from normal control subjects were treated with DEX and vitD as indicated in methods. ³H-thymidine was added to the medium 18h before collecting the cells. Cell division was estimated based on ³H-thymidine incorporation (n=4).