Effect of vitamin D(3) on the antimicrobial activity of human airway surface liquid: preliminary results of a randomised placebo-controlled double-blind trial

INTRODUCTION: Vitamin D(3) supplementation has been reported to prevent lung infections and increase the gene expression of antimicrobial peptides such as cathelicidin. We investigated the effect of vitamin D(3) supplementation on the antimicrobial activity of airway surface liquid (ASL) in human subjects. Since smoking can increase the risk of respiratory infections, we also investigated the effect of smoking in the cathelicidin response to vitamin D(3) in human airway epithelia in vitro. METHODS: This study is a subanalysis of single-centre community-based randomised placebo-controlled double-blind trial. Participants were randomised to receive 1000 international units per day of oral vitamin D(3) or identical placebo for 90 days. Blood and ASL samples were collected preintervention and postintervention. 105 participants were originally enrolled, 86 completed the trial, and due to low protein concentration in the samples, 40 participants were finally analysed. Our primary outcome was ASL antimicrobial activity. We also considered secondary outcomes including changes in serum concentration of 25-hydroxyvitamin D(3) (25(OH)D(3)), 1,25-hydroxyvitamin D(3), calcium and parathyroid hormone (PTH). In addition, we studied the effect of cigarette smoke extract (CSE) exposure to primary human airway epithelial cell cultures on the gene expression of cathelicidin in response to vitamin D(3) and expression of CYP27B1 (1-alpha hydroxylase), responsible for vitamin D(3) activation. RESULTS: Vitamin D(3) supplementation significantly increased both ASL antimicrobial activity and serum concentration of 25(OH)D(3). In a subgroup analysis, we found that smokers did not increase their baseline antimicrobial activity in response to vitamin D(3). Exposure to CSE on human airway epithelia decreased baseline CYP27B1 gene expression and cathelicidin response to 25(OH)D(3). CONCLUSION: Vitamin D(3) supplementation for 90 days increases ASL antimicrobial activity. Data from this preliminary study suggest that smoking may alter the ability of airway epithelia to activate vitamin D(3) and increase the gene expression of cathelicidin antimicrobial peptide. TRIAL REGISTRATION NUMBER: NCT01967628; Post-results.