Longitudinal Lung Function Changes--Aging/Genetics/Risk

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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.