Role of vitamin D in asthma

The prevalence of asthma has been increasing in parallel with trends in vitamin D deficiency. Some researchers have suggested a causal link between vitamin D deficiency and the development of asthma [1], while others have suggested vitamin D supplementation, rather than deficiency, as the link [2,3]. Wjst et al. published two ground-breaking articles concerning the relationship between the increase in asthma and allergy prevalence and the start of vitamin D supplementation in foods. These articles suggested that supplementation of vitamin D has a potential causal role in increased asthma prevalence [2,3]. By contrast, Litonjua and Weiss were among the first to suggest vitamin D deficiency due to an affluent life spent mainly indoors as a causative factor for increased asthma and allergy prevalence [1]. Reasons for vitamin D deficiency occurring despite recommendations of supplementation include increased time spent indoors in industrialized countries, and the use of sunscreen and covering when outside to offset risks of skin cancer. Therefore, researchers have begun to examine the roles and functions of vitamin D in an attempt to clarify its possible association to asthma. The metabolism of vitamin D from sunlight, as well as dietary sources, will be explained. A review of studies examining vitamin D levels will be explored in an effort to show the relationship between lower vitamin D levels and less asthma control, even in individuals with apparent high sunlight exposure. Asthma is a complex disease with multiple postulated pathogenic mechanisms. How these mechanisms could relate to vitamin D will be summarized briefly later, reviewing the genetics of the vitamin D receptor (VDR) and vitamin D and the relationship with the immune system, particularly the Th1 and Th2 responses. In the allergic asthma phenotype, there is an increase in Th2 cytokines, such as IL-4, IL-13 and IL-5, which are important for IgE synthesis and eosinophilia in the airways. There is also a phenotype that involves neutrophilic infiltration of the airways, with Th17 cells producing IL-23 and IL-17. Furthermore, there has been an established link between CD4CD25 regulatory T cells (Tregs) and asthma. An x-linked deficiency in these cells causing immunodysregulation, polyendrocrinopathy and enteropathy (IPEX) leads to an increase in autoimmune and allergic diseases. This helped establish the role of Tregs in allergic asthma. When functioning normally, CD4CD25 Tregs will suppress Th2 responses, inhibiting cytokine release and the allergic asthma response. This role may be defective or overcome by allergen-driven pathways in patients with allergic disease. Therefore, the ability to restore CD4CD25 Treg function could be a potential therapeutic goal in allergic asthma patients [4]. The role of vitamin D in restoring CD4CD25 Tregs will be discussed later. The interaction of vitamin D with bronchial smooth muscle, including its role in inflammation, will be discussed, with a separate discussion on the impact of vitamin D on respiratory infections. The role of vitamin D in patients with steroid-insensitive asthma is also discussed, as well as other aspects of the relationship of asthma and vitamin D, such as the association of vitamin D and asthma onset, and vitamin D and asthma control. Asthma is a prevalent disease that leads to high morbidity and healthcare costs. The search for prevention and better treatment strategies is ongoing. Vitamin D deficiency has been shown to occur commonly and is associated with poorer asthma control measures. As the understanding of the biological effects of vitamin D emerges, there appears to be strong evidence for an important role of vitamin D in the respiratory and immune systems. Discovering the complexities of the functions of vitamin D may extend the possibilities of vitamin D use to include prevention and/or treatment of asthma. This article explores what is known about vitamin D, and its known and potential role in asthma.