Patients with cystic fibrosis (CF) suffer from chronic lung infection and inflammation leading to respiratory failure. Vitamin D deficiency is common in patients with CF, and correction of vitamin D deficiency may improve innate immunity and reduce inflammation in patients with CF. We conducted a double-blinded, placebo-controlled, randomized clinical trial of high-dose vitamin D to assess the impact of vitamin D therapy on antimicrobial peptide concentrations and markers of inflammation. We randomized 30 adults with CF hospitalized with a pulmonary exacerbation to 250 000 IU of cholecalciferol or placebo, and evaluated changes in plasma concentrations of inflammatory markers and the antimicrobial peptide LL-37 at baseline and 12 weeks post intervention. In the vitamin D group, there was a 50.4% reduction in tumor necrosis factor-α (TNF-α) at 12 weeks (P<0.01), and there was a trend for a 64.5% reduction in interleukin-6 (IL-6) (P = 0.09). There were no significant changes in IL-1β, IL-8, IL-10, IL-18BP and NGAL (neutrophil gelatinase-associated lipocalin). We conclude that a large bolus dose of vitamin D is associated with reductions in two inflammatory cytokines, IL-6 and TNF-α. This study supports the concept that vitamin D may help regulate inflammation in CF, and that further research is needed to elucidate the potential mechanisms involved and the impact on clinical outcomes.

Cystic fibrosis (CF) lung disease is characterized by airway inflammation and leads to respiratory failure. Vitamin D (VD) insufficiency occurs in up to 90% of CF patients. Since VD is thought to have anti‐inflammatory properties, we evaluated the impact of VD on markers of inflammation in CF adults hospitalized with a pulmonary exacerbation (PEx).30 CF adults admitted for a PEx were randomized to a single 250,000 IU oral dose of VD3 or placebo. Serum 25‐hydroxyVD (25D), IL‐6 and TNF‐α concentrations were measured on admission, at 1 week and 12 weeks.A single, high dose of VD resulted in a significant increase in 25D at 1 week and decrease in TNFα at 12 weeks; there was also a trend for decreased IL‐6 at 1 week compared to placebo. The mean changes (table) were accompanied by 32.2 more hospital‐free days (p = 0.04) and 32.5 more IV antibiotic therapy‐free days (p = 0.07) in the VD group compared to placebo.High dose VD in CF adults is associated with a decrease in markers of inflammation and an increase in hospital‐free days. VD should be evaluated as adjunct therapy for severe CF pulmonary exacerbations.Grant Funding Source : Cystic Fibrosis Foundation, National Institutes of Health, BTR Group