Vitamin D deficiency is associated with pulmonary dysfunction in cystic fibrosis

Sexauer, William; Hadeh, Anas; Ohman‐Strickland, Pamela; Zanni, Robert; Varlotta, Laurie; Holsclaw, Douglas S.; Fiel, Stanley B.; Graff, Gavin R.; Atlas, Arthur B.; Bisberg, Dorothy; Hadjiliadis, Denis; Michel, Suzanne H.; Mintz, Daria; Chakraborty, Rupak; Marra, Bridget; Lomas, Paula; Ward, Tara L.; Sassman, Meagen; Imbesi, Giovanna; Kitch, Diane; Mallowe, Allison M.

doi:10.1016/j.jcf.2014.12.006

Cited by 56 publications

(66 citation statements)

References 32 publications

(39 reference statements)

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“…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].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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Vitamin D has immunomodulatory properties in the defence against pathogens. Its insufficiency is a widespread feature of cystic fibrosis (CF) patients, which are repeatedly suffering from rhinovirus (RV)-induced pulmonary exacerbations.To investigate whether vitamin D has antiviral activity, primary bronchial epithelial cells from CF children were pre-treated with vitamin D and infected with RV16. Antiviral and anti-inflammatory activity of vitamin D was assessed. RV and LL-37 levels were measured in bronchoalveolar lavage (BAL) of CF children infected with RV.Vitamin D reduced RV16 load in a dose-dependent manner in CF cells (

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Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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“…2,3 In addition to its importance for bone health, vitamin D acts as a potent immune modulatory agent with complex effects. 4,5 In CF, vitamin D concentrations have been associated with lung function, 2,6 annual number of pulmonary exacerbations 7 and with total serum IgG levels. 2 The current recommendations for vitamin D supplementation in CF were designed with focus on bone health.…”

Section: Introductionmentioning

confidence: 99%

Clinical impact of vitamin D treatment in cystic fibrosis: a pilot randomized, controlled trial

et al. 2016

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BACKGROUND/OBJECTIVES: Vitamin D insufficiency in cystic fibrosis is common. Vitamin D3 is currently preferred over D2. We aimed to study the efficacy of vitamin D2 and D3 at increasing serum 25-hydroxyvitamin D (s25OHD) concentrations and their effect on respiratory health in cystic fibrosis. SUBJECTS/METHODS: Sixteen CF patients were randomized to receive vitamin D2 or D3 or to serve as controls. The starting dose of 5000 IU (o 16 years old) or 7143 IU/day (⩾16 years old) was further individually adjusted. Three months of intervention were followed by two of washout (ClinicalTrials.gov NCT01321905). RESULTS: To increase s25OHD, the mean daily dose of vitamin D2 and D3 had to be increased up to 15650 and 8184 IU, respectively. The combined group of vitamin D2 and D3 treated patients decreased plasma IL-8 (Po 0.05). Patients provided vitamin D3 improved FVC at the end of the trial (P o 0.05). Change in s25OHD was positively correlated with changes in the adult Quality-of-Life respiratory score at the end of supplementation (P = 0.006, r = 0.90), and with changes in FEV1 (P = 0.042, r = 0.62) and FVC (P = 0.036, r = 0.63) at one month of washout. CONCLUSIONS: Vitamin D supplementation may contribute to reduced inflammation and improved lung function in CF.

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“…Moreover, for CF patients hospitalized with a pulmonary exacerbation, a bolus dose of vitamin D is associated with reduced levels of the inflammatory cytokines TNF-α and IL-6. On the other hand, serum 25(OH)D levels are significantly associated with pulmonary dysfunction in CF patients [35].…”

Section: Discussionmentioning

confidence: 99%

Inflammation and Oxidation Biomarkers in Patients with Cystic Fibrosis: The Influence of Azithromycin

Olveira¹,

Padilla²,

Dorado³

et al. 2017

Eurasian J Med

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Objective: In addition to their antibiotic effect, macrolides appear to modulate the inflammatory response in cystic fibrosis (CF) and could influence oxidative stress. The objective of this study was to assess oxidation biomarkers and levels of inflammation and to determine whether there is an association between these parameters and the intake of macrolides. Materials and Methods:The subjects included in this cross-sectional study were, on the one hand, clinically stable patients with CF and, on the other, healthy controls. The following serum and plasma inflammatory and oxidative stress biomarkers were measured: interleukin-6 (IL-6), reactive C protein (RCP), tumor necrosis alpha (TNF-α), glutathione peroxidase (GPx), total antioxidant capacity (TAC), catalase (CAT), and superoxide dismutase (SOD), together with markers of lipid peroxidation (8-isoprostanes and thiobarbituric acid reactive substances [TBARS]). Clinical, anthropometric, lung function, radiological, and analytical variables (albumin, prealbumin, vitamins, and zinc) were also recorded. Results:We studied 36 adults with CF and 41 controls. No differences were observed in age, gender, or anthropometric variables. The patients had significantly higher levels of IL-6, TNF-α, RCP, TBARS, and isoprostanes, and lower levels of SOD than the controls. Twenty-three of the patients were treated with azithromycin, and they had more severe clinical and radiological parameters than those who were not but nevertheless presented significantly lower levels of TNF-α. No differences were observed in the markers of oxidation.Conclusion: Inflammation and oxidation biomarkers were increased in patients with CF compared with controls. The use of azithromycin was associated with reduced TNF-α levels and did not influence oxidation parameters.

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Vitamin D deficiency is associated with pulmonary dysfunction in cystic fibrosis

Abstract: Serum 25(OH)D levels are significantly associated with pulmonary function in CF. Further study is required to determine whether this association is causal.

Cited by 56 publications

References 32 publications

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

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

Clinical impact of vitamin D treatment in cystic fibrosis: a pilot randomized, controlled trial

Inflammation and Oxidation Biomarkers in Patients with Cystic Fibrosis: The Influence of Azithromycin

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