Fish Oil Intake, Biomarkers and Change in Lung Function

描述（由申请人提供）：我们最近在护士健康研究中使用经过验证的、基于问卷的鱼油摄入和COPD定义，观察到鱼油摄入对慢性阻塞性肺疾病（COPD）发展的潜在保护作用。当前应用程序的主要目的是通过更精确的暴露和结果测量来复制这一有希望的发现，并调查557名老年、现在和以前的吸烟者中潜在的分子和遗传中介。主要假设为：1)膳食鱼摄入量和n-3 PUFA水平与纵向肺功能下降和CT肺密度呈负相关；2) n-3 PUFA水平与白三烯(LT)-B4、肿瘤坏死因子(TNF)- α、干扰素(IFN)- γ和可溶性粘附分子等生物中介呈负相关，这些中介在n-3 PUFA水平与肺功能下降之间的因果通路上；3)相关基因变异，如编码tnf - α、ICAM-1和一氧化氮合酶（NOS）亚型的基因变异，可识别肺功能下降风险较高的个体。已经收集了557名参与者的基线问卷、肺活量测定、胸部CT数据和血液标本，目前正在进行为期一年的问卷、肺活量测定和胸部CT测量随访。我们建议通过延长4年的随访，在这一老年、曾经和现在的吸烟者队列中研究上述假设；总共六项措施将产生足够的力量来检验鱼类摄入量、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。使用现有的队列和先前收集的血液样本将为这种潜在的有前途和安全的COPD治疗提供相对具有成本效益的结果。

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.