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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. 补充维生素 D 可降低曲霉菌致敏的 CF 患者特异性 Th2 反应:一项一期开放标签研究。
Pub Date : 2015-01-01 Epub Date: 2015-06-04 DOI: 10.1186/s40733-015-0003-5
Nikki Lynn Hue Nguyen, Joseph M Pilewski, Juan C Celedón, Sivanarayana Mandalapu, Megan L Blanchard, Adrienne DeRicco, Elizabeth Hartigan, John F Alcorn, Jay K Kolls

Background: Patients with cystic fibrosis (CF) complicated by allergic bronchopulmonary aspergillosis (ABPA) are vitamin D deficient and in vitro treatment with 1,25 (OH)2 vitamin D3 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 D3 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 D3 (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, FEV1, urinary calcium/creatinine ratio, and cytokine production by Aspergillus-stimulated peripheral blood T cells.

Results: Six months of vitamin D3 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 D3 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.

Trial registration: This trial was registered at www.clinicaltrials.gov as NCT01222273.

背景:囊性纤维化(CF)并发过敏性支气管肺曲霉菌病(ABPA)的患者缺乏维生素D,用1,25 (OH)2 维生素D3对ABPA的CF患者的CD4+细胞进行体外处理可降低曲霉菌(Af)诱导的Th2反应。这项 I 期临床试验研究了在患有 ABPA 的 CF 患者中每日补充维生素 D3 以减少过敏反应和 ABPA 症状并提高血清维生素 D 水平的安全性和有效性:7名年龄在12岁及以上、临床诊断为CF和ABPA且目前有Af致敏证据的患者每天服用4000 IU维生素D3(胆钙化醇),连续服用24周。研究的主要结果是安全性,其次是 CD4+ T 细胞中曲霉菌诱导的 IL-13 反应,以检验维生素 D 补充剂是否安全并能减少 CD4+ T 细胞中曲霉菌诱导的 IL-13 反应这一假设。次要结果包括总IgE、曲霉菌特异性IgE、维生素D水平、FEV1、尿钙/肌酐比值以及曲霉菌刺激外周血T细胞产生的细胞因子:补充维生素 D3 6 个月后,血清 25-(OH) 维生素 D 水平显著提高,治疗耐受性良好,未发现维生素 D 毒性或高钙血症。没有出现严重的不良反应。每日补充维生素D可使曲霉菌诱导的IL-13反应在基线访问和24周访问之间显著降低(p = 0.04)。每日补充维生素 D 8 周(p = 0.035)和 24 周(p = 0.04)后,曲霉菌特异性 IgE 水平也明显下降:结论:对于有 ABPA 病史且目前有证据表明对曲霉菌具有 Th2 免疫力的 CF 患者来说,在 24 周内每天补充 4000 IU 维生素 D3 的耐受性良好。.每日补充维生素 D 与减少曲霉菌诱导的外周 IL-13 反应有关。.CD4+T细胞和曲霉菌特异性IgE水平,以及血清维生素D水平的增加。这种治疗方法的耐受性良好,该研究支持进一步研究在Th2介导的疾病中使用维生素D补充剂:该试验已在 www.clinicaltrials.gov 登记为 NCT01222273。
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