Targeting Vitamin D Deficiency to Limit Exacerbations in Respiratory Diseases: Utopia or Strategy With Potential?

Background: Vitamin D deficiency has been shown to be independently associated with increased risk of viral acute respiratory infection (ARI) in a number of observational studies, and meta-analysis of clinical trials of vitamin D supplementation for prevention of ARI has demonstrated protective effects. Several cellular studies have investigated the effects of vitamin D metabolites on immune responses to respiratory viruses, but syntheses of these reports are lacking. Scope: In this article, we review the literature reporting results of in vitro experiments investigating immunomodulatory actions of vitamin D metabolites in human respiratory epithelial cells infected with respiratory viruses. Key findings: Vitamin D metabolites do not consistently influence replication or clearance of rhinovirus, respiratory syncytial virus (RSV) or influenza A virus in human respiratory epithelial cell culture, although they do modulate expression and secretion of type 1 interferon, chemokines including CXCL8 and CXCL10 and pro-inflammatory cytokines, such as TNF and IL-6. Future research: More studies are needed to clarify the effects of vitamin D metabolites on respiratory virus-induced expression of cell surface markers mediating viral entry and bacterial adhesion to respiratory epithelial cells.

The aim of the present study is to summarize existing literature on vitamin D levels in adults in different continents and different countries worldwide. The best determinant of vitamin D status is the serum concentration of 25-hydroxyvitamin D (25(OH)D). Most investigators agree that serum 25(OH)D should be higher than 50 nmol/l, but some recommend higher serum levels. Traditional risk groups for vitamin D deficiency include pregnant women, children, older persons, the institutionalized, and non-western immigrants. This chapter shows that serum 25(OH)D levels are not only suboptimal in specific risk groups, but also in adults in many countries. Especially, in the Middle-East and Asia, vitamin D deficiency in adults is highly prevalent. Copyright © 2011 Elsevier Ltd. All rights reserved.

Low serum 25-hydroxyvitamin D (25-[OH]D) levels have been associated with lower FEV(1), impaired immunologic control, and increased airway inflammation. Because many patients with chronic obstructive pulmonary disease (COPD) have vitamin D deficiency, effects of vitamin D supplementation may extend beyond preventing osteoporosis. To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations. Randomized, single-center, double-blind, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00666367) University Hospitals Leuven, Leuven, Belgium. 182 patients with moderate to very severe COPD and a history of recent exacerbations. 100,000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year. The primary outcome was time to first exacerbation. Secondary outcomes were exacerbation rate, time to first hospitalization, time to second exacerbation, FEV(1), quality of life, and death. Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group (mean between-group difference, 30 ng/mL [95% CI, 27 to 33 ng/mL]; P < 0.001). The median time to first exacerbation did not significantly differ between the groups (hazard ratio, 1.1 [CI, 0.82 to 1.56]; P = 0.41), nor did exacerbation rates, FEV(1), hospitalization, quality of life, and death. However, a post hoc analysis in 30 participants with severe vitamin D deficiency (serum 25-[OH]D levels <10 ng/mL) at baseline showed a significant reduction in exacerbations in the vitamin D group (rate ratio, 0.57 [CI, 0.33 to 0.98]; P = 0.042). This was a single-center study with a small sample size. High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations. In participants with severe vitamin D deficiency at baseline, supplementation may reduce exacerbations. Applied Biomedical Research Program, Agency for Innovation by Science and Technology (IWT-TBM).