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

描述（由研究者提供）：COPD和肺炎是60岁及以上成人发病和死亡的主要原因，COPD患者的肺炎发生率更高。成人哮喘常与COPD并存，并可导致COPD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）和大多数导致COPD进展的COPD其他合并症（例如，呼吸道感染/肺炎、肌无力、心力衰竭）可能受益于维生素D补充疗法，但这需要严格的测试。海洋ω-3脂肪酸通过与维生素D不同的途径调节炎症。我们已经仔细评估了每种补充剂的剂量，以达到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可以预防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，以评估维生素D和海洋ω-3脂肪酸补充剂对COPD和哮喘急性发作，气流阻塞和肺功能下降以及肺炎风险的潜在益处或风险。我们建议利用大规模随机临床试验-维生素D和OmegA-3 TriaL（VITAL），其终点是癌症和心血管疾病的一级预防-进行维生素D和长链海洋omega-3多不饱和脂肪酸（二十碳五烯酸[EPA]加二十二碳六烯酸[DHA]）补充剂对阻塞性和传染性呼吸道疾病结局的作用的首次主要评估。VITAL是一项成本效益、随机、双盲、安慰剂对照的临床试验，在20，000名基线时无癌症或CVD的男性和女性中进行，仅根据年龄（男性60岁，女性65岁）进行选择，对黑人进行过采样。在2x2析因设计中，受试者将被随机分配至中高剂量维生素D3（胆钙化醇; 1600 IU [40 5g]/d）和鱼油（EPA [500 mg/d] + DHA [500 mg/d]）补充剂（或安慰剂）。我们假设维生素D3和海洋ω-3脂肪酸（EPA+DHA）补充剂将导致COPD和哮喘恶化的减少;肺功能下降的减少;气道阻塞和哮喘控制的改善;以及成人肺炎的减少。 为了检验我们的肺部VITAL假设，必须完成对基线呼吸系统症状状态、过去一年的COPD和哮喘急性发作、哮喘控制和控制药物和急救药物的使用、肺功能以及基线维生素D和脂肪酸水平的随机化前评估。因此，与计划于2010年1月开始的母试验VITAL（附录B）的入组期平行进行该辅助研究至关重要。

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.