Longitudinal Lung Function Changes--Aging/Genetics/Risk

描述(申请人提供)：低肺功能是慢性阻塞性肺疾病(COPD)的中心特征，也是美国发病率和死亡率的重要原因。此外，肺功能低下与糖尿病和心血管疾病等各种疾病有关，并与全因死亡有关。尽管吸烟仍然是低肺功能和COPD的最大危险因素，但只有少数吸烟者出现临床公认的低肺功能和COPD。此外，大约6%-10%的普通人群有未被认识到的肺功能低下。因此，更好地了解与低肺功能相关的危险因素是必要的。由于炎症标记物即使在健康的衰老中也被认为是升高的，我们假设炎症机制是衰老和肺功能下降的共同原因。作为对这种RFA的回应，我们打算对肺功能变化进行纵向分析，这一队列已经被跟踪了大约30年。我们将研究全身炎症标志物在衰老过程中对肺功能下降的影响。由于对吸烟的反应有很大的差异，我们还假设对吸烟和其他炎性刺激的反应是由遗传变异改变的。我们将研究参与这些炎症途径的基因(例如，IL[IL]-6、IL-10、IL-2和肿瘤坏死因子[TNF]-α)对肺功能减退率的影响。这一建议的结果将阐明影响衰老过程中肺功能下降的潜在机制。

DESCRIPTION (provided by applicant): Low lung function is a central characteristic of chronic obstructive pulmonary disease (COPD), an important cause of morbidity and mortality in the United States. Furthermore, low lung function has been associated with various diseases such as diabetes and cardiovascular disorders, and is associated with all-cause mortality. Although smoking remains the strongest risk factor for low lung function and COPD, only a minority of smokers develop clinically recognized low lung function and COPD. Furthermore, about 6- 10% of the general population have unrecognized low lung function. Thus, a better understanding of the risk factors associated with low lung function is necessary. Since inflammatory markers are seen to be elevated even in healthy aging, we hypothesize that inflammatory mechanisms are common to both aging and lung function decline. In response to this RFA, we intend to perform longitudinal analyses of lung function change, in a cohort that has been followed for about 30 years. We will investigate systemic markers of inflammation for their effect on lung function decline in aging. Because there is great variation in the response to smoking, we also hypothesize that response to smoking and other inflammatory stimuli are modified by genetic variation. We will study genes that participate in these inflammatory pathways (e.g. interleukin[IL]-6, IL-10, IL-2, and tumor necrosis factor[TNF]-alpha) for their effect on rates of lung function decline. The results of this proposal will shed light on potential mechanisms that affect lung function decline in aging.