Fish Oil Intake, Biomarkers and Change in Lung Function

鱼油摄入量、生物标志物和肺功能的变化

• 批准号: 6712570
• 负责人: R Graham BARR
• 金额: $ 64.3万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6712570
• 关键词: biomarker; cell adhesion molecules; chemoprevention; chronic obstructive pulmonary disease; clinical research; dietary lipid; human subject; interferon gamma; leukotrienes; longitudinal human study; lung; lung neoplasms; marine animal oil; nitric oxide synthase; nutrient intake activity; pathologic process; respiratory function; spirometry; tumor necrosis factor alpha; unsaturated fatty acids

DESCRIPTION (provided by applicant): We have recently observed a potentially protective effect of fish oil intake on the development of chronic obstructive pulmonary disease (COPD) using validated, questionnaire-based definitions of fish oil intake and COPD in the Nurses' Health Study. The primary aims of the current application are to replicate this promising finding with more precise measures of exposures and outcomes and to investigate potential molecular and genetic intermediaries in a population of 557 older, current and former smokers. The main hypotheses are: 1) dietary fish intake and n-3 PUFA levels are inversely associated with longitudinal lung function decline and CT lung density; 2) n-3 PUFA levels are inversely associated with biological intermediaries, such as leukotriene (LT)-B4, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and soluble adhesion molecules, and these intermediaries are on the causal pathway between n-3 PUFA levels and lung function decline; 3) related genes variants, such as those in genes coding for TNF-alpha, ICAM-1 and nitric oxide synthase (NOS) isoforms, identify individuals at higher risk of lung function decline. Baseline questionnaire, spirometry, and chest CT data and blood specimens have been collected for 557 participants, and one-year follow-up visits for questionnaire, spirometry and chest CT measures are currently ongoing. We propose to study the above hypotheses in this cohort of older, former and current smokers by extending follow-up for an additional four years; the total of six measures would yield adequate power to examine the important relationships between fish intake, n-3 polyunsaturated fatty acids (PUFA), inflammatory mediators, related gene variants and longitudinal lung function. Use of this existing cohort with previously collected blood samples will provide relatively cost-effective results about this potentially promising and safe therapy for COPD.

描述(由申请人提供)：我们最近在《护士健康研究》中通过对鱼油摄入量和慢性阻塞性肺疾病(COPD)的有效、基于问卷的定义，观察到鱼油摄入量对慢性阻塞性肺疾病(COPD)的潜在保护作用。目前应用的主要目的是用更精确的暴露和结果测量来复制这一有希望的发现，并在557名老年、现任和曾经吸烟者中调查潜在的分子和遗传中介。主要假设是：1)饮食鱼类摄入量和n-3PUFA水平与纵向肺功能下降和CT肺密度呈负相关；2)n-3PUFA水平与生物中介物质，如白三烯(LT)-B4、肿瘤坏死因子(TNF)-α、干扰素(IFN)-γ和可溶性黏附分子呈负相关，这些中介分子处于n-3PUFA水平与肺功能下降之间的因果路径上；3)相关基因变体，如编码TNF-α、ICAM-1和一氧化氮合酶(NOS)亚型的基因，识别出肺功能下降的风险更高的个体。已经收集了557名参与者的基线问卷、肺活量测定、胸部CT数据和血液样本，目前正在进行为期一年的问卷调查、肺活量测定和胸部CT措施的随访。我们建议在这组年龄较大、曾经吸烟者和现在吸烟者中研究上述假设，将再延长四年的随访时间；总共六项措施将产生足够的力量来检查鱼类摄入量、n-3多不饱和脂肪酸(PUFA)、炎症介质、相关基因变异和纵向肺功能之间的重要关系。使用现有的队列和以前采集的血液样本将提供关于这种潜在的有希望的安全的COPD治疗方法的相对成本效益的结果。