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

SynopsisThis review examines the scientific evidence behind the hypothesis that vitamin D plays a role in the pathogenesis of allergic diseases, with a particular focus on emerging data regarding vitamin D and atopic dermatitis. Both elucidated molecular interactions of vitamin D with components of the immune system, as well as clinical data regarding vitamin D deficiency and atopic diseases are discussed. The rationale behind the "sunshine hypothesis," laboratory evidence supporting links between vitamin D deficiency and allergic diseases, the clinical evidence for/and against vitamin D playing a role in allergic diseases, and the emerging evidence regarding the potential use of vitamin D in augmentation of the innate immune response in atopic dermatitis are reviewed. KeywordsVitamin D; atopic dermatitis; asthma; allergy IntroductionObservations by Palm in 1890 and Sniadecki in 1922 of the lower prevalence of rickets in equatorial and rural populations respectively prompted both investigators to hypothesize that sun exposure was the reason for such a difference [1][2][3]. Subsequent work by Mellanby established cod liver oil as a cure for dogs with rickets [4] and experiments by McCollum demonstrated the existence of a vitamin within cod liver oil [5]. Both cod liver oil and sunlight exposure became known as treatment modalities for rickets. Foods containing cholesterol that were irradiated with light were also shown to cure rickets. Windhaus and colleagues subsequently discovered a cholesterol precursor, 7-dehydrocholesterol (7-DHC). Their Nobel Prize winning work showed that irradiation of 7-DHC with UV light induced formation of vitamin D 3 [1,6].Humans receive at least 80% of their vitamin D through UV induced skin production [7,8]. According to the Environmental Protection Agency's National Human Activity Pattern Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptImmunol Allergy Clin North Am. Author manuscript; available in PMC 2011 August 1. [19,23]. The scientific evidence for this hypothesis will be reviewed. Vitamin D MetabolismVitamin D enters the body through either the skin via cutaneous conversion of 7-DHC into pre-vitamin D 3 or the gut via food and/or supplement ingestion (see Figure 1) The Effects of Vitamin D on the Immune System Vitamin D and AllergySeveral large birth cohort studies have examined the relationship between infant vitamin D supplementation and subsequent development of allergy and asthma. One study looked at a segment of the Northern Finland Birth Cohort from 1966 in which infants were supplemented with ...

Background the effects of serum vitamin D status on atopy, steroid requirement and functional responsiveness to corticosteroids in children vs. adults with asthma have not been studied systematically. Objective to explore age-specific effects of vitamin D in asthma. Methods serum vitamin D levels were examined in a prospective study of adults and children (102 normal controls and 103 asthmatics). Peripheral blood mononuclear cells (PBMC) were cultured for 3h +/−100nM dexamethasone (DEX) and the expression of corticosteroid-regulated genes was detected by real time PCR. Serum IgE levels were measured; information about asthmatics’ steroid requirement was collected. Results 47.6% of asthmatics and 56.8% normal control subjects had deficient serum vitamin D levels (<20ng/ml) with mean ± SD of 20.7±9.8ng/ml and 19.2±7.7ng/ml, respectively. In multivariate regression models, a significant positive correlation between serum vitamin D and the expression of vitamin D regulated targets - cyp24a by PBMC (p=0.0084, pediatric asthma group only) and serum LL-37 levels (p=0.0006, pediatric; but p=0.0067 in adult asthma groups) was found. An inverse association between vitamin D and serum IgE levels was observed in the pediatric (p=0.006) asthma group. Serum vitamin D (p=0.05) as well as PBMC cyp24a expression (p=0.0312) demonstrated significant inverse relationship with daily ICS dose in the pediatric asthma group only. Cyp24a expression in PBMC correlated positively with in vitro suppression of TNFα (p=0.05) and IL-13 (p=0.0094) in PBMC by DEX only in the pediatric asthma group. Conclusions this study demonstrated significant associations between serum vitamin D status and steroid requirement and in vitro responsiveness to corticosteroids in the pediatric but not the adult asthma group. Vitamin D was also related to IgE levels in children but not in adults. Clinical Implication The results of this study suggest that vitamin D supplementation in children may enhance corticosteroid responses, control atopy and could thereby improve asthma control.

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