title: Vitamin D supplementation decreasesAspergillus fumigatusspecific Th2 responses in CF patients with aspergillus sensitization: a phase one open-label study.
abstract: BACKGROUND
  Patients with cystic fibrosis (CF) complicated by allergic bronchopulmonary aspergillosis (ABPA) are vitamin D deficient andin vitrotreatment with 1,25 (OH)2vitamin D3of CD4+ cells from CF patients with ABPA decreasesAspergillus fumigatus(Af)-induced Th2 responses. This Phase I clinical trial investigated the safety and effectiveness of daily vitamin D3supplementation 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 D3(cholecalciferol) daily for 24 weeks. The primary outcome of the study was safety followed by theAspergillusinduced IL-13 response in CD4+ T cells to test the hypothesis that vitamin D supplementation is safe and reducesAspergillusinduced IL-13 responses in CD4+ T cells. Secondary outcomes included total IgE,Aspergillus-specific IgE, vitamin D levels, FEV1, urinary calcium/creatinine ratio, and cytokine production byAspergillus-stimulated peripheral blood T cells.
  
  
  RESULTS
  Six months of vitamin D3supplementation 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 decreasedAspergillusinduced 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 D3daily 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 reducedAspergillusinduced IL-13 responses from peripheral. . CD4+ T cells andAspergillus-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.
  
  
  BACKGROUND
  This trial was registered at www.clinicaltrials.gov as NCT01222273.
authors.affiliation: Division of Infectious Diseases, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA; Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.
authors.forename: Nikki Lynn Hue
authors.initials: NL
authors.lastname: Nguyen
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Antonio J and Janet Palumbo Cystic Fibrosis Center, Children's Hospital of Pittsburgh of UPMC, Rangos Research Building, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Pilewski
authors.affiliation: Antonio J and Janet Palumbo Cystic Fibrosis Center, Children's Hospital of Pittsburgh of UPMC, Rangos Research Building, 4401 Penn Avenue, Pittsburgh, PA 15224, USA; Department of Pediatrics, Division of Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh of UPMC, Rangos Research Building, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Celedón
authors.affiliation: Department of Pediatrics, Division of Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh of UPMC, Rangos Research Building, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
authors.forename: Sivanarayana
authors.initials: S
authors.lastname: Mandalapu
authors.affiliation: Department of Pediatrics, Division of Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh of UPMC, Rangos Research Building, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Blanchard
authors.affiliation: Antonio J and Janet Palumbo Cystic Fibrosis Center, Children's Hospital of Pittsburgh of UPMC, Rangos Research Building, 4401 Penn Avenue, Pittsburgh, PA 15224, USA; Department of Pediatrics, Division of Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh of UPMC, Rangos Research Building, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
authors.forename: Adrienne
authors.initials: A
authors.lastname: DeRicco
authors.affiliation: Antonio J and Janet Palumbo Cystic Fibrosis Center, Children's Hospital of Pittsburgh of UPMC, Rangos Research Building, 4401 Penn Avenue, Pittsburgh, PA 15224, USA; Department of Pediatrics, Division of Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh of UPMC, Rangos Research Building, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hartigan
authors.affiliation: Department of Pediatrics, Division of Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh of UPMC, Rangos Research Building, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Alcorn
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
keywords: Allergic bronchopulmonary aspergillosis; Cystic fibrosis; Vitamin D