维生素D3对低维生素D水平且有症状的成人哮喘患者治疗失败的影响 VIDA随机临床试验
2015/02/25
摘要
重要性：在哮喘和其他疾病中，维生素D的缺乏与不良结局相关。然而，对于缺乏维生素D的哮喘患者在吸入糖皮质激素的基础上，同时口服维生素D3是否可以改善不良结局，仍不十分清楚。
目的：评估对低维生素水平且有症状的哮喘患者补充维生素D是否可以提高吸入糖皮质激素的临床疗效。
试验设计和受试者：VIDA（维生素D的附加治疗增强哮喘的激素反应性）是一个随机、双盲、平行分组、安慰剂对照试验，受试者为有症状的成人哮喘患者，并且血浆维生素D的水平低于30ng/ml。 该试验是在国立心肺血管机构哮喘网的9个医疗中心进行，从2011年4月开始注册到2014年1月完成随访。在接受吸入糖皮质激素治疗的导入期后，408例患者随机化进入试验。
干预措施：在吸入环索奈德（320ug/d）基础上，口服维生素D3（首次100 000IU，随后4000IU/d，持续28周；n=201）或安慰剂（n=207）。如果在治疗12周后哮喘得到控制，环索奈德减量至160ug/d, 持续使用8周，如果哮喘仍能得到控制，继续将环索奈德减量至80ug/d，再持续使用8周。
主要的结局指标：主要结局指标为第一次哮喘治疗失败的时间（一个反映肺功能降低并且需要增加使用β-受体激动剂、全身糖皮质激素以及卫生保健的综合指标）。
结果：在28周的治疗期加用维生素D3并没用改变第一次治疗失败率（维生素D3组为28%[95%CI, 21%-34%]和安慰剂组为 29%[95%CI, 23%-35%]，校正后的风险比为 0.9 [95%CI, 0.6-1.3]）。在14个预设的次要结局指标中，分析了包括哮喘急性发作在内的9个结局指标，其中唯一有统计学意义的结局指标是为了达到哮喘控制，使用环索奈德的总剂量两组间具有微小差异（维生素D3组111.3 μg/d [95%CI, 102.2-120.4 μg/d]，安慰剂组126.2 μg/d [95%CI,117.2-135.3 μg/d]，差异为14.9 μg/d [95%CI, 2.1-27.7 μg/d] ）。
结论和相关性：维生素D3并没有降低缺乏维生素D且为持续期哮喘患者的第一次治疗失败率或急性发作率。我们的结果并不支持对有症状的哮喘患者补充维生素D3的治疗方案。
Effect of Vitamin D3 on Asthma Treatment Failures in Adults With Symptomatic Asthma and Lower Vitamin D Levels The VIDA Randomized Clinical Trial
Mario C, Tonya S, Susan J. K, Michael D. C, Loren D, Fernando H, Shamsah D. K,
Wendy C. M, J, Christine A. S, Pedro A, MD; Leonard B. B, Eugene B, Homer A. B, James C, AnneM. F, Deborah G, Mandeep H, Elliot I, Monica K, Jerry A. K, Craig L, Stephen C. L, Robert L, Njira L, Richard J.M, David T.M, Edward N, Stephen P. P, Wanda P, Loretta G. Q, Ajay S, Lewis S, Julian S, Lisa S, Kaharu S, Michael E.W, Sally W, Steven R.W, E. Rand S, for the National Heart, Lung, and Blood Institute’s AsthmaNet
ABSTRACT
IMPORTANCE In asthma and other diseases, vitamin D insufficiency is associated with adverse outcomes. It is not known if supplementing inhaled corticosteroids with oral vitamin D3 improves outcomes in patients with asthma and vitamin D insufficiency.
OBJECTIVE To evaluate if vitamin D supplementation would improve the clinical efficacy of inhaled corticosteroids in patients with symptomatic asthma and lower vitamin D levels.
DESIGN, SETTING, AND PARTICIPANTS The VIDA (Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma) randomized, double-blind, parallel, placebo-controlled trial studying adult patients with symptomatic asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL was conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute’s AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by January 2014. After a run-in period that included treatment with an inhaled corticosteroid, 408 patients were randomized.
INTERVENTIONS Oral vitamin D3 (100 000 IU once, then 4000 IU/d for 28 weeks; n = 201) or placebo (n = 207) was added to inhaled ciclesonide (320 μg/d). If asthma control was achieved after 12 weeks, ciclesonide was tapered to 160 μg/d for 8 weeks, then to 80 μg/d for 8 weeks if asthma control was maintained.
MAIN OUTCOMES AND MEASURES The primary outcome was time to first asthma treatment failure (a composite outcome of decline in lung function and increases in use of β-agonists, systemic corticosteroids, and health care).
RESULTS Treatment with vitamin D3 did not alter the rate of first treatment failure during 28 weeks (28%[95%CI, 21%-34%] with vitamin D3 vs 29%[95%CI, 23%-35%] with placebo; adjusted hazard ratio, 0.9 [95%CI, 0.6-1.3]). Of 14 prespecified secondary outcomes, 9 were analyzed, including asthma exacerbation; of those 9, the only statistically significant outcome was a small difference in the overall dose of ciclesonide required to maintain asthma control (111.3 μg/d [95%CI, 102.2-120.4 μg/d] in the vitamin D3 group vs 126.2 μg/d [95%CI, 117.2-135.3 μg/d] in the placebo group; difference of 14.9 μg/d [95%CI, 2.1-27.7 μg/d]).
CONCLUSIONS AND RELEVANCE Vitamin D3 did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency. These findings do not support a strategy of therapeutic vitamin D3 supplementation in patients with symptomatic asthma.
JAMA; 2014;311(20);2083-2091
重要性：在哮喘和其他疾病中，维生素D的缺乏与不良结局相关。然而，对于缺乏维生素D的哮喘患者在吸入糖皮质激素的基础上，同时口服维生素D3是否可以改善不良结局，仍不十分清楚。
目的：评估对低维生素水平且有症状的哮喘患者补充维生素D是否可以提高吸入糖皮质激素的临床疗效。
试验设计和受试者：VIDA（维生素D的附加治疗增强哮喘的激素反应性）是一个随机、双盲、平行分组、安慰剂对照试验，受试者为有症状的成人哮喘患者，并且血浆维生素D的水平低于30ng/ml。 该试验是在国立心肺血管机构哮喘网的9个医疗中心进行，从2011年4月开始注册到2014年1月完成随访。在接受吸入糖皮质激素治疗的导入期后，408例患者随机化进入试验。
干预措施：在吸入环索奈德（320ug/d）基础上，口服维生素D3（首次100 000IU，随后4000IU/d，持续28周；n=201）或安慰剂（n=207）。如果在治疗12周后哮喘得到控制，环索奈德减量至160ug/d, 持续使用8周，如果哮喘仍能得到控制，继续将环索奈德减量至80ug/d，再持续使用8周。
主要的结局指标：主要结局指标为第一次哮喘治疗失败的时间（一个反映肺功能降低并且需要增加使用β-受体激动剂、全身糖皮质激素以及卫生保健的综合指标）。
结果：在28周的治疗期加用维生素D3并没用改变第一次治疗失败率（维生素D3组为28%[95%CI, 21%-34%]和安慰剂组为 29%[95%CI, 23%-35%]，校正后的风险比为 0.9 [95%CI, 0.6-1.3]）。在14个预设的次要结局指标中，分析了包括哮喘急性发作在内的9个结局指标，其中唯一有统计学意义的结局指标是为了达到哮喘控制，使用环索奈德的总剂量两组间具有微小差异（维生素D3组111.3 μg/d [95%CI, 102.2-120.4 μg/d]，安慰剂组126.2 μg/d [95%CI,117.2-135.3 μg/d]，差异为14.9 μg/d [95%CI, 2.1-27.7 μg/d] ）。
结论和相关性：维生素D3并没有降低缺乏维生素D且为持续期哮喘患者的第一次治疗失败率或急性发作率。我们的结果并不支持对有症状的哮喘患者补充维生素D3的治疗方案。
(刘影1 张红萍1 王刚1 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（JAMA; 2014;311(20);2083-2091)
（JAMA; 2014;311(20);2083-2091)
Effect of Vitamin D3 on Asthma Treatment Failures in Adults With Symptomatic Asthma and Lower Vitamin D Levels The VIDA Randomized Clinical Trial
Mario C, Tonya S, Susan J. K, Michael D. C, Loren D, Fernando H, Shamsah D. K,
Wendy C. M, J, Christine A. S, Pedro A, MD; Leonard B. B, Eugene B, Homer A. B, James C, AnneM. F, Deborah G, Mandeep H, Elliot I, Monica K, Jerry A. K, Craig L, Stephen C. L, Robert L, Njira L, Richard J.M, David T.M, Edward N, Stephen P. P, Wanda P, Loretta G. Q, Ajay S, Lewis S, Julian S, Lisa S, Kaharu S, Michael E.W, Sally W, Steven R.W, E. Rand S, for the National Heart, Lung, and Blood Institute’s AsthmaNet
ABSTRACT
IMPORTANCE In asthma and other diseases, vitamin D insufficiency is associated with adverse outcomes. It is not known if supplementing inhaled corticosteroids with oral vitamin D3 improves outcomes in patients with asthma and vitamin D insufficiency.
OBJECTIVE To evaluate if vitamin D supplementation would improve the clinical efficacy of inhaled corticosteroids in patients with symptomatic asthma and lower vitamin D levels.
DESIGN, SETTING, AND PARTICIPANTS The VIDA (Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma) randomized, double-blind, parallel, placebo-controlled trial studying adult patients with symptomatic asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL was conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute’s AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by January 2014. After a run-in period that included treatment with an inhaled corticosteroid, 408 patients were randomized.
INTERVENTIONS Oral vitamin D3 (100 000 IU once, then 4000 IU/d for 28 weeks; n = 201) or placebo (n = 207) was added to inhaled ciclesonide (320 μg/d). If asthma control was achieved after 12 weeks, ciclesonide was tapered to 160 μg/d for 8 weeks, then to 80 μg/d for 8 weeks if asthma control was maintained.
MAIN OUTCOMES AND MEASURES The primary outcome was time to first asthma treatment failure (a composite outcome of decline in lung function and increases in use of β-agonists, systemic corticosteroids, and health care).
RESULTS Treatment with vitamin D3 did not alter the rate of first treatment failure during 28 weeks (28%[95%CI, 21%-34%] with vitamin D3 vs 29%[95%CI, 23%-35%] with placebo; adjusted hazard ratio, 0.9 [95%CI, 0.6-1.3]). Of 14 prespecified secondary outcomes, 9 were analyzed, including asthma exacerbation; of those 9, the only statistically significant outcome was a small difference in the overall dose of ciclesonide required to maintain asthma control (111.3 μg/d [95%CI, 102.2-120.4 μg/d] in the vitamin D3 group vs 126.2 μg/d [95%CI, 117.2-135.3 μg/d] in the placebo group; difference of 14.9 μg/d [95%CI, 2.1-27.7 μg/d]).
CONCLUSIONS AND RELEVANCE Vitamin D3 did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency. These findings do not support a strategy of therapeutic vitamin D3 supplementation in patients with symptomatic asthma.
JAMA; 2014;311(20);2083-2091
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