Diet, Biomarkers and Lung Function

描述（由申请人提供）：本提案是一份关于老龄化研究职业发展奖（K08）的申请。申请人是一名接受过医学和营养流行病学培训的新研究员。申请人的研究将集中在低肺功能的营养决定因素。随着年龄的增长，肺功能逐渐恶化，老年人肺功能衰退加速。肺功能低下是老年人死亡率的独立预测因子。肺功能低下的主要临床表现是慢性阻塞性肺疾病（COPD），是美国第四大死因。慢性阻塞性肺病患病率和死亡率正在上升，但除了避免吸烟之外，几乎没有可用的预防策略。饮食可能在预防肺功能加速衰退和慢性阻塞性肺病方面发挥重要作用。目前的提案将作为一个桥梁，在呼吸疾病和衰老的营养和遗传流行病学的独立调查员的职业生涯。职业发展/培训活动包括在流行病学研究的设计和实施方面的指导进步，以及关于衰老、肺功能、遗传学和遗传学统计建模的会议/实验室培训/课程工作，以及资助。研究计划将包括：1)收集主要数据，验证多民族动脉粥样硬化研究（MESA）食物频率问卷（FFQ）项目；2) MESA和心血管健康研究(CHS)/AII-Stars研究中两种饮食因素（促氧化剂和抗氧化剂）以及相关生化标志物和基因变异与肺功能和肺密度的相关性研究。本提案将测试以下假设：A) MESA FFQ在估算亚硝酸盐/硝酸盐和腌肉的摄入量方面是有效的；B) MESA患者大量摄入亚硝酸盐/硝酸盐和腌肉以及血浆3-硝基酪氨酸（3-NT）水平升高与肺功能降低、肺密度降低和肺密度纵向下降较大相关；C) MESA患者大量摄入维生素D和乳制品以及25（OH）维生素D水平升高与较高的肺功能、较高的肺密度和较慢的肺密度纵向下降有关；D)高腊肉摄入量与更大程度的肺功能纵向下降有关，高乳制品摄入量与CHS患者肺功能纵向下降较慢有关；E)参与一氧化氮（或亚硝酸盐）产生途径的基因变异（iNOS、imf - α、il -1 β、ifn - γ、VEGF和NF-kappaB）和编码维生素d结合蛋白的基因变异与MESA患者的肺功能和肺密度以及肺密度的纵向变化有关。该研究计划有可能阐明一种新型膳食氧化剂和抗氧化剂在预防与年龄相关的肺功能下降和慢性阻塞性肺病中的作用。该提案将为候选人在饮食、饮食相关基因以及肺功能和COPD中基因-饮食相互作用的R01成功应用做好准备。

DESCRIPTION (provided by applicant): The current proposal is an application for a Career Development Award in aging research (K08). The applicant is a new researcher with training in medicine and nutritional epidemiology. The applicant's research will focus on the nutritional determinants of low lung function. Lung function deteriorates gradually with increasing age and lung function decline is accelerated in older adults. Low lung function is an independent predictor of mortality among the elderly. The major clinical manifestation of low lung function, chronic obstructive pulmonary disease (COPD), is the fourth leading cause of death in the United States. COPD prevalence and mortality are increasing, but few preventive strategies are available other than avoidance of smoking. Diet may play an important role in the prevention of accelerated lung function decline and COPD. The current proposal will serve as a bridge to an independent investigator career in the nutritional and genetic epidemiology of respiratory disease and aging. The career development/training activities include mentored advancement in the design and implementation of epidemiological studies, and conferences/lab training/course work on aging, lung function, genetics and statistical modeling in genetics, and grantsmanship. The research proposal will include: 1) primary data collection to validate the Multi-Ethnic Study of Atherosclerosis (MESA) food frequency questionniare (FFQ) items; and 2) investigation of associations of two dietary factors (a pro-oxidant and an anti-oxidant) and related biochemical markers and gene variants with lung function and lung density in the MESA and the Cardiovascular Health Study (CHS)/AII-Stars Study. This proposal will be testing the following hypotheses: A) the MESA FFQ is valid in estimating intake of nitrite/nitrate and cured meats; B) high intake of nitrite/nitrate and cured meats and elevated plasma levels of 3-nitrotyrosine (3-NT) are associated with lower lung function, lower lung density, and greater longitudinal decline in lung density in MESA; C) high intake of vitamin D and dairy products and elevated levels of 25(OH) vitamin D are associated with higher lung function, higher lung density, and slower longitudinal decline in lung density in MESA; D) high cured meat intake is associated with greater longitudinal decline in lung function, and high dairy intake is associated with slower longitudinal decline in lung function in CHS; and E) variants of genes involved in the nitric oxide (or nitrite) production pathway (iNOS, IMF-alpha, IL-1beta, IFN-gamma, VEGF, and NF-kappaB) and encoding vitamin D-binding protein are associated with lung function and lung density and longitudinal change in lung density in MESA. The research plan has the potential to elucidate the role of a novel dietary oxidant and antioxidant in the prevention of age-related decline in lung function and COPD. This proposal will prepare the candidate well to apply successfully for R01 on diet, diet-related genes, and gene-diet interactions in lung function and COPD.