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

描述（由研究者提供）：COPD和肺炎是60岁及以上成年人发病和死亡的主要原因，COPD患者的肺炎发病率更高。成人哮喘常与COPD共存，并使COPD恶化。目前治疗慢性阻塞性肺病的方式有限，维生素D缺乏症的患病率很高。慢性阻塞性肺病（COPD、哮喘、气流阻塞）和大多数导致慢性阻塞性肺病进展的慢性阻塞性肺病附加合并症（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脂肪酸通过维生素D的不同途径来调节炎症。我们仔细评估了每一种补充剂的剂量，以达到疗效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omega-3脂肪酸补充剂对慢性阻塞性肺病和哮喘加重、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进行首次主要评估。VITAL是一项具有成本效益的、随机的、双盲的、安慰剂对照的临床试验，在2万名基线时没有癌症或心血管疾病的男性和女性中进行，受试者仅按年龄选择（男性60岁，女性65岁），并以黑人为过样本。在2x2因子设计中，参与者将被随机分配到中至高剂量维生素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）。我们假设补充维生素D3和海洋omega-3脂肪酸（EPA+DHA）将导致COPD和哮喘恶化的减少；减轻肺功能衰退；改善气道阻塞，控制哮喘；减少成人肺炎的发生。为了验证我们的Lung VITAL假设，有必要完成对过去一年的基线呼吸症状状态、COPD和哮喘加重的预随机化评估；哮喘控制及控制器和抢救药物的使用；肺功能;维生素D和脂肪酸的基线水平因此，这项辅助研究与预定于2010年1月开始的母体VITAL试验（附录B）的入组期同时进行是至关重要的。

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. PUBLIC HEALTH RELEVANCE: Chronic obstructive lung disease (COPD) and pneumonia are leading causes of death in United States and world-wide. COPD, which is also a significant source of disability, is increasing in prevalence. Approximately 14 million adults have asthma, which leads to approximately 12 million missed work days per year in the United States. In adults, COPD and asthma often coexist. If vitamin D or marine omega-3 fatty acid supplementation reduce COPD and asthma exacerbations, reduce decline of lung function, improve asthma control and/or reduce pneumonia risk, this would be of great benefit to public health.