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Vitamin D supplementation decreases Aspergillus fumigatus specific Th2 responses in CF patients with aspergillus sensitization: A phase one open-label study

Nguyen, NLH and Pilewski, JM and Celedón, JC and Mandalapu, S and Blanchard, ML and DeRicco, A and Hartigan, E and Alcorn, JF and Kolls, JK (2015) Vitamin D supplementation decreases Aspergillus fumigatus specific Th2 responses in CF patients with aspergillus sensitization: A phase one open-label study. Asthma Research and Practice, 1 (1).

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Abstract

Background: Patients with cystic fibrosis (CF) complicated by allergic bronchopulmonary aspergillosis (ABPA) are vitamin D deficient and in vitro treatment with 1,25 (OH) vitamin D of CD4+ cells from CF patients with ABPA decreases Aspergillus fumigatus(Af)-induced Th2 responses. This Phase I clinical trial investigated the safety and effectiveness of daily vitamin D supplementation in CF patients with ABPA to reduce allergic responses and ABPA symptoms, and increase serum vitamin D levels. Methods: Seven patients ages 12 years and older with a clinical diagnosis of CF and ABPA with current evidence of Af sensitization received 4000 IU vitamin D (cholecalciferol) daily for 24 weeks. The primary outcome of the study was safety followed by the Aspergillus induced IL-13 response in CD4+ T cells to test the hypothesis that vitamin D supplementation is safe and reduces Aspergillus induced IL-13 responses in CD4+ T cells. Secondary outcomes included total IgE, Aspergillus- specific IgE, vitamin D levels, FEV , urinary calcium/creatinine ratio, and cytokine production by Aspergillus-stimulated peripheral blood T cells. Results: Six months of vitamin D supplementation resulted in significant increases in serum 25-(OH) vitamin D level, and the treatment was well tolerated without evidence of vitamin D toxicity or hypercalcemia. There were no serious adverse events. Daily vitamin D supplementation led to significantly decreased Aspergillus induced IL-13 responses between the baseline visit and that at 24 weeks (p = 0.04). Aspergillus-specific IgE level was also significantly decreased after 8 (p = 0.035) and 24 weeks of daily vitamin D supplementation (p = 0.04). Conclusions: 4000 IU vitamin D daily over a 24-week period is well tolerated in CF patients with a history ABPA and current evidence of Th2 immunity to Af. Daily vitamin D supplementation was associated with reduced Aspergillus induced IL-13 responses from peripheral. CD4+ T cells and Aspergillus-specific IgE levels, as well as increased serum vitamin D levels. This treatment was well tolerated and the study supports further investigation of the use of vitamin D supplementation in Th2 mediated diseases. 2 3 3 3 1 3 3


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Nguyen, NLH
Pilewski, JMpilewski@pitt.eduPILEWSKI
Celedón, JC
Mandalapu, S
Blanchard, ML
DeRicco, A
Hartigan, Eerh49@pitt.eduERH49
Alcorn, JFjfa9@pitt.eduJFA9
Kolls, JK
Date: 1 January 2015
Date Type: Publication
Journal or Publication Title: Asthma Research and Practice
Volume: 1
Number: 1
DOI or Unique Handle: 10.1186/s40733-015-0003-5
Schools and Programs: School of Medicine > Critical Care Medicine
School of Medicine > Immunology
School of Medicine > Infectious Diseases and Microbiology
School of Medicine > Pediatrics
Refereed: Yes
Date Deposited: 17 Aug 2016 13:21
Last Modified: 31 Mar 2021 12:55
URI: http://d-scholarship.pitt.edu/id/eprint/29261

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