Pilot study of vitamin D supplementation in adults with cystic fibrosis pulmonary exacerbation

Abstract

<u>Background:</u> Vitamin D insufficiency is common in cystic fibrosis (CF) and vitamin D repletion may have an important role in improving clinical outcomes in CF. This randomized, placebo-controlled, pilot study examined the feasibility and impact of a single, large dose of cholecalciferol on vitamin D status and clinical outcomes in subjects with CF. <u>Methods:</u> Thirty adults with were randomized in a double-blinded, pilot study to receive 250,000 IU cholecalciferol or placebo within 48 h of hospital admission for a pulmonary exacerbation. Concentrations of 25-hydroxyvitamin D (25(OH)D), clinical outcomes and potential adverse events were assessed up to one year after randomization. Mixed effects linear regression models were used to evaluate the difference in mean serum concentrations and log-rank analyses were used to evaluate survival. <u>Results:</u> Data from all subjects was analyzed. Serum 25(OH)D concentrations increased from a mean of 30.6 ± 3.2 ng/mL to 58.1 ± 3.5 ng/mL (p < 0.001) at one week and 36.7 ± 2.6 ng/mL by 12 weeks (p = 0.06) in the vitamin D group; in contrast, serum 25(OH)D concentrations remained unchanged in the placebo group. Unadjusted, one-year survival and hospital-free days were increased in the vitamin D group (p = 0.029, p = 0.036; respectively). There was also a trend toward increased IV antibiotic therapy-free days in the vitamin D group (p = 0.073). There were no signs of hypervitaminosis D or adverse events. Serum PTH and calcium concentrations were similar across both groups. <u>Conclusions:</u> In this pilot study, a single, oral bolus of cholecalciferol increased serum 25(OH)D concentrations and was associated with a trend toward improved clinical outcomes in CF subjects hospitalized for a pulmonary exacerbation. Further investigation is needed into the clinical impact of improved vitamin D status in patients with CF.

Vitamin D Deficiency Is Associated with Pulmonary Exacerbations in Children with Cystic Fibrosis

“…In infants, it has been shown that low vitamin D in cord blood samples at birth is associated with higher incidence of respiratory syncytial virus (6), and infants readmitted to the neonatal intensive care unit with acute lower respiratory tract infection had lower vitamin D levels than age-matched control subjects (7). In adults with CF, those who received a high dose of cholecalciferol (250,000 IU) once at the time of admission for a pulmonary exacerbation had significantly fewer hospitalizations for pulmonary exacerbations over the next 6 months compared with those receiving placebo (36). Combined, these studies suggest that vitamin D may prevent viral infection and possibly work as an adjunct treatment to antibiotics to decrease the severity of an exacerbation.…”

Vitamin D represses rhinovirus replication in cystic fibrosis cells by inducing LL-37

“…The AMPs contain vitamin D-responsive elements (VDRE) in their gene promoter, whereby vitamin D is directly inducing LL-37 and β-defensin gene expressions [34]. Furthermore, a positive correlation between serum vitamin D levels and lung function [41] in CF patients as well as improved clinical outcomes in CF patients with pulmonary exacerbation have been demonstrated [42].…”

Dietary intake and nutritional status of micronutrients in adults with cystic fibrosis in relation to current recommendations

“…Evidence for extra-skeletal functions of vitamin D in CF is accumulating. For example, vitamin D is likely to improve respiratory function through its role in antimicrobial peptide and cytokine production and its association with muscle strength [40,41,43,44]. It is also associated with CFRD through potential involvement in islet function regulation, insulin production and secretion, and insulin sensitivity [42,46].…”

“…PTH, concurrent with serum calcium, phosphorus and 1,25(OH) 2 D itself, tightly regulates serum 1,25(OH) 2 D levels. Absorption and metabolism of vitamin D seem to vary according to supplement formulation as well [44,46,48,52,53]. Animal-derived cholecalciferol (vitamin D 3 ) [53] appears to outperform plant-derived ergocalciferol (vitamin D 2 ) [48,52,54] at much lower dosages in normalising serum 25(OH)D levels in adults with CF.…”