Lung VITamin D and OmegA-3 TriaL (Lung VITAL)

描述(由调查人员提供)：慢性阻塞性肺病和肺炎是60岁及以上成年人发病率和死亡率的主要原因之一，而患有慢性阻塞性肺病的人肺炎的发病率更高。在成人中，哮喘经常与COPD并存，并会加剧COPD的进展。目前治疗COPD的方法有限，维生素D缺乏症的患病率很高。COPD肺部疾病(COPD、哮喘、气流阻塞)以及导致COPD进展的大多数COPD其他并发症(如呼吸道感染/肺炎、肌肉无力、心力衰竭)可能受益于维生素D补充治疗，但这需要严格的测试。海洋omega-3脂肪酸通过从维生素D到调节炎症的不同途径发挥作用。我们已经仔细评估了每种补充剂的剂量，以实现有效性和安全性的最佳平衡。观察性研究和临床试验表明，食用鱼类和EPA或DHA可能会预防COPD、哮喘或肺炎，但数据并不一致。因此，有一个令人信服的理由进行临床试验，以评估补充维生素D和海洋omega-3脂肪酸对COPD和哮喘加重、气流阻塞和肺功能下降以及肺炎风险的潜在益处或风险。我们建议利用一项大规模随机临床试验--维生素D和omega-3试验(VITAL)，其终点是癌症和心血管疾病的一级预防--对补充维生素D和长链海洋omega-3多不饱和脂肪酸(二十碳五烯酸[EPA]和二十二碳六烯酸[DHA])的作用进行首次重大评估。VITAL是一项成本效益高、随机、双盲、安慰剂对照的临床试验，在基线水平上没有癌症或心血管疾病的2万名男性和女性中进行选择，他们只根据年龄(男性年龄为60岁，女性年龄为65岁)进行选择，黑人样本过多。在2x2析因设计中，参与者将被随机分配到中到高剂量的维生素D3(胆钙化醇；1600IU[40 5g]/d)和鱼油(EPA[500 mg/d]DHA[500 mg/d])补充剂(或安慰剂)。我们假设，补充维生素D3和海洋欧米茄-3脂肪酸(EPA DHA)将导致COPD和哮喘恶化的减少；肺功能下降的减少；呼吸道阻塞和哮喘控制的改善；以及成人肺炎的减少。为了检验我们的肺活量假设，必须完成对基线呼吸道症状状态、COPD和过去一年中哮喘恶化情况、哮喘控制和控制器和抢救药物的使用、肺功能以及基线维生素D和脂肪酸水平的预随机评估。因此，至关重要的是，这项辅助研究应与定于2010年1月开始的家长重要试验(附录B)的登记期间同时进行。

DESCRIPTION (provided by investigator): COPD and pneumonia are among the leading causes of morbidity and mortality in adults 60 years and older, and pneumonia rates are higher for those with COPD. Asthma often coexists with COPD in adults and worsens COPD progression. The current modalities for treatment of COPD are limited, and prevalence of vitamin D deficiency is high. COPD lung disease (COPD, asthma, airflow obstruction), and most COPD additional co-morbidities responsible for COPD progression (e.g., respiratory infections/pneumonia, muscle weakness, cardiac failure) may benefit from vitamin D supplementation therapy but this requires rigorous testing. Marine omega-3 fatty acids work through different pathways from vitamin D to modulate inflammation. We have carefully evaluated the dose of each of these supplements to achieve the best balance of efficacy and safety. Observational studies and clinical trials suggest that fish consumption and EPA or DHA may protect against COPD, asthma or pneumonia, but data are not consistent. Thus there is a compelling rationale for a clinical trial to evaluate the potential benefits or risks of vitamin D and marine omega-3 fatty acid supplementation on COPD and asthma exacerbations, airflow obstruction and decline of lung function, and risk of pneumonia. We propose to take advantage of a large-scale randomized clinical trial-the VITamin D and OmegA-3 TriaL (VITAL), whose endpoints are primary prevention of cancer and cardiovascular diseases-to conduct the first major evaluation of the role of vitamin D and long-chain marine omega-3 polyunsaturated fatty acid (eicosapentaenoic acid [EPA] plus docosahexaenoic acid [DHA]) supplementation on obstructive and infectious respiratory disease outcomes. VITAL is a cost-effective, randomized, double-blind, placebo- controlled clinical trial among 20,000 men and women without cancer or CVD at baseline, who are selected on age only (men aged e60 and women aged e65), with an oversampling of blacks. In a 2x2 factorial design, participants will be randomized to moderate-to-high dose vitamin D3 (cholecalciferol; 1600 IU [40 5g]/d) and fish oil (EPA [500 mg/d] + DHA [500 mg/d]) supplements (or placebos) independently. We hypothesize that Vitamin D3 and marine omega-3 fatty acid (EPA+DHA) supplementation will result in reduction of COPD and asthma exacerbations; in reduction in decline of lung function; in improvement of airway obstruction and asthma control; and in reduction of pneumonia in adults. To test our Lung VITAL hypotheses it is essential to complete pre-randomization assessment of baseline respiratory symptom status, COPD and asthma exacerbations in the past year; asthma control and use of controller and rescue medication; pulmonary function; and baseline vitamin D and fatty acid levels. Thus it is critically important that this ancillary study be undertaken in parallel to the enrollment period for the parent VITAL trial (Appendix B), which is scheduled to begin in January 2010.