Vitamin D and Bronchial Asthma: An Overview of Data From the Past 5 Years.

PURPOSE: Vitamin D is a potent immunomodulator capable of dampening inflammatory signals in several cell types involved in the asthmatic response. Its deficiency has been associated with increased inflammation, exacerbations, and overall poor outcomes in patients with asthma. Given the increase in the prevalence of asthma over the past few decades, there has been enormous interest in the use of vitamin D supplementation as a potential therapeutic option. Here, we critically reviewed the most recent findings from in vitro studies, animal models, and clinical trials regarding the role of vitamin D in treating bronchial asthma. METHODS: Using the key terms [Vitamin D, asthma, clinical trials, in vivo and in vitro studies], the [PubMed, Google Scholar] databases were searched for [clinical trials, original research articles, meta-analyses, and reviews], English-language articles published from [2012] to the present. Articles that were [Articles that did not meet these criteria were excluded] excluded from the analysis. FINDINGS: Several studies have found that low serum levels of vitamin D (< 20 ng/mL) are associated with increased exacerbations, increased airway inflammation, decreased lung function, and poor prognosis in asthmatic patients. Results from in vitro and in vivo studies in animals and humans have suggested that supplementation with vitamin D may ameliorate several hallmark features of asthma. However, the findings obtained from clinical trials are controversial and do not unequivocally support a beneficial role of vitamin D in asthma. Largely, interventional studies in children, pregnant women, and adults have primarily found little to no effect of vitamin D supplementation on improved asthma symptoms, onset, or progression of the disease. This could be related to the severity of the disease process and other confounding factors. IMPLICATIONS: Despite the conflicting data obtained from clinical trials, vitamin D deficiency may influence the inflammatory response in the airways. Further studies are needed to determine the exact mechanisms by which vitamin D supplementation may induce antiinflammatory effects.

Vitamin D Supplementation Reduces Induction of Epithelial-Mesenchymal Transition in Allergen Sensitized and Challenged Mice.

Asthma is a chronic disease of the lung associated with airway hyperresponsiveness (AHR), airway obstruction and airway remodeling. Airway remodeling involves differentiation of airway epithelial cells into myofibroblasts via epithelial-mesenchymal transition (EMT) to intensify the degree of subepithelial fibrosis. EMT involves loss in E-cadherin with an increase in mesenchymal markers, including vimentin and N-cadherin. There is growing evidence that vitamin D has immunomodulatory and anti-inflammatory properties. However, the underlying molecular mechanisms of these effects are still unclear. In this study, we examined the contribution of vitamin D on the AHR, airway inflammation and expression of EMT markers in the airways of mice sensitized and challenged with a combination of clinically relevant allergens, house dust mite, ragweed, and Alternaria (HRA). Female Balb/c mice were fed with vitamin D-sufficient (2000 IU/kg) or vitamin D-supplemented (10,000 IU/kg) diet followed by sensitization with HRA. The density of inflammatory cells in the bronchoalveolar lavage fluid (BALF), lung histology, and expression of EMT markers by immunofluorescence were examined. Vitamin D-supplementation decreased AHR, airway inflammation in the BALF and the features of airway remodeling compared to vitamin D-sufficiency in HRA-sensitized and -challenged mice. This was accompanied with increased expression of E-cadherin and decreased vimentin and N-cadherin expression in the airways. These results indicate that vitamin D may be a beneficial adjunct in the treatment regime in allergic asthma.

The impact of vitamin D on asthmatic human airway smooth muscle.

Asthma is a chronic heterogeneous disorder, which involves airway inflammation, airway hyperresponsiveness (AHR) and airway remodeling. The airway smooth muscle (ASM) bundle regulates the broncho-motor tone and plays a critical role in AHR as well as orchestrating inflammation. Vitamin D deficiency has been linked to increased severity and exacerbations of symptoms in asthmatic patients. It has been shown to modulate both immune and structural cells, including ASM cells, in inflammatory diseases. Given that current asthma therapies have not been successful in reversing airway remodeling, vitamin D supplementation as a potential therapeutic option has gained a great deal of attention. Here, we highlight the potential immunomodulatory properties of vitamin D in regulating ASM function and airway inflammation in bronchial asthma.