Vitamin D and asthma.

REVIEW Dermato-Endocrinology 4:2, 137–145; April/May/June 2012; G 2012 Landes Bioscience Vitamin D and asthma Sheena D. Brown,1 H. Hardie Calvert1 and Anne M. Fitzpatrick1,2,* 1 Department of Pediatrics; Emory University; Atlanta, GA USA; 2Children’s Healthcare of Atlanta Center for Developmental Lung Biology; Atlanta, GA USA Keywords: vitamin D, asthma, asthma prevalence, children, inflammation Abbreviations: 25(OH)D, 25-hydroxyvitamin D3; IgE, immunoglobulin E; IL, interleukin; TH2, T-helper cell type-2; UVB, ultraviolet-B; VDR, vitamin D receptor Asthma, one of the most prevalent diseases affecting people worldwide, is a chronic respiratory disease characterized by heightened airway inflammation, airway hyperresponsiveness and airflow obstruction in response to specific triggers. While the specific mechanisms responsible for asthma are not well understood, changing environmental factors associated with urban lifestyles may underlie the increased prevalence of the disorder. Vitamin D is of particular interest in asthma since vitamin D concentrations decrease with increased time spent indoors, decreased exposure to sunlight, less exercise, obesity, and inadequate calcium intake. Additionally, a growing body of literature suggests that there is a relationship between vitamin D status and respiratory symptoms, presumably through immunomodulatory effects of vitamin D. This review discusses vitamin D as it relates to asthma across the age spectrum, with a focus on human studies. . e nc process involves smooth muscle hypertrophy, epithelial gobletcell hyperplasia and permanent deposition of airway extracellular matrix proteins which may ultimately increase airflow obstruction and the respiratory symptom burden of the disorder.9 Within industrialized Westernized countries, the prevalence of asthma has steadily increased by 25% to 75% per decade since 1960, causing it to become a major public health concern.10-12 The increased prevalence of asthma may be influenced by changing environmental factors associated with urban lifestyles. Indeed, numerous dietary hypotheses have been proposed.13-15 Among the nutrients and antioxidants included in this hypothesis, vitamin D is of particular interest since vitamin D concentrations decrease with increased time spent indoors, decreased exposure to sunlight, less exercise, obesity, and inadequate calcium intake.16 Additionally, a growing body of literature suggests that there is a relationship between vitamin D status and asthma-related respiratory symptoms,17-22 presumably through the immunomodulatory effects of vitamin D.23,24 This brief review discusses vitamin D as it relates to asthma across the age spectrum, with a focus on emerging human studies over the past decade. A literature review was performed for relevant publications spanning from 2002 to present. Publications were limited to those indexed on PubMed and written in English. Searches were made for “vitamin D” and “asthma,” excluding in vitro and animal studies. Relevant articles identified from this search are discussed below. e i c s o i B . e s t e u d b i n r a t L s i 2 d 1 t 0 o 2 n o © D Introduction Asthma, one of the most prevalent diseases affecting people worldwide, is a chronic respiratory disease characterized by heightened airway inflammation, airway hyperresponsiveness and airflow obstruction in response to specific triggers (Fig. 1). Common symptoms include chest tightness, wheezing, cough and difficulty breathing, which are commonly treated with two different classes of medications: inhaled corticosteroids, used as a daily controller medication, and β-adrenergic agonists, which are used to induce bronchodilation.1 While the specific mechanisms responsible for asthma are poorly understood, in part due to the marked heterogeneity of the disorder in both adults2 and children,3 numerous aberrant immune responses are clearly associated with the disorder.4 For example, T-helper cell type-2 (TH2) cytokines, such as interleukin (IL)-4, IL-5, and IL-13, are upregulated in the asthmatic airway and are associated with increased eosinophilia,5,6 mast cell degranulation7 and increased levels of immunoglobulin E (IgE).6,7 Impairment of immunogenic tolerance, along with complex interactions between cells and inflammatory mediators, ultimately promotes airway injury in a process commonly referred to as airway “remodeling.”8 This *Correspondence to: Anne M. Fitzpatrick; Email: Submitted: 01/20/12; Revised: 04/16/12; Accepted: 04/18/12 http://dx.doi.org/10.4161/derm.20434 www.landesbioscience.com Vitamin D Overview Vitamin D, a fat-soluble nutrient, is a secosteroid hormone which is widely recognized as a modulator of calcium absorption and bone health and further regulates neuromuscular function, cellular differentiation, insulin secretion, and blood pressure.25,26 Vitamin D also plays an important role in immune regulation through interactions between 1,25-dihydroxyvitamin D and vitamin D receptors (VDRs). VDRs are expressed on a variety of airway immune cells, where they function as classic nuclear steroid hormone receptors and ultimately regulate the transcription of numerous genes associated with inflammation and immunomodulation.27 Vitamin D also plays an important role in respiratory infection by facilitating Toll-like receptor signaling through increased synthesis of human cathelicidin antimicrobial peptide,28-30 which is cleaved to generate the active cationic peptide, LL-37.31,32 Vitamin D also exerts direct effects on target Dermato-Endocrinology 137 previously associated with vitamin D deficiency in epidemiologic studies.41-43 Vitamin D thresholds. Serum concentrations of 25(OH)D are considered to be a biomarker and indicator of vitamin D status.44,45 Although vitamin D insufficiency has traditionally been defined as a serum 25(OH)D concentration of 20 to 29 ng/mL,46 a panel of experts from the Institute of Medicine recently suggested that vitamin D insufficiency be redefined as a serum 25(OH)D concentration less than 20 ng/mL.47 This recommendation was based on inconclusive evidence for the threshold of 29 ng/mL and evidence for adverse skeletal effects at thresholds less than 20 ng/mL.47 However, this revised definition of vitamin D insufficiency has generated significant controversy48,49 and thus there is presently no universally accepted definition for “optimal” 25(OH)D concentrations independent of musculoskeletal health. . e nc e i c s o i B . e s t e u d b i n r a t L s i 2 d 1 t 0 o 2 n o © D Maternal/Infant Vitamin D Exposure and Childhood Respiratory Symptoms Figure 1. Airway inflammation associated with asthma. The rapid increase in asthma prevalence within Westernized countries is unlikely solely due to genetics. Instead, a number of environmental exposures may also alter the rate of asthma development.50-54 Of these modifiable environmental exposures, the role of diet in asthma is of particular interest13,55 since recent studies (...truncated)