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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG027014-01
Application #
7008256
Study Section
Special Emphasis Panel (ZRG1-HOP-R (50))
Program Officer
Dutta, Chhanda
Project Start
2005-09-30
Project End
2009-08-31
Budget Start
2005-09-30
Budget End
2006-08-31
Support Year
1
Fiscal Year
2005
Total Cost
$396,891
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Hanson, Corrine; Lyden, Elizabeth; Furtado, Jeremy et al. (2016) Serum tocopherol levels and vitamin E intake are associated with lung function in the normative aging study. Clin Nutr 35:169-74
Poon, Audrey H; Houseman, E Andres; Ryan, Louise et al. (2014) Variants of asthma and chronic obstructive pulmonary disease genes and lung function decline in aging. J Gerontol A Biol Sci Med Sci 69:907-13
Litonjua, Augusto A (2012) Vitamin D deficiency as a risk factor for childhood allergic disease and asthma. Curr Opin Allergy Clin Immunol 12:179-85
Lange, Nancy E; Sparrow, David; Vokonas, Pantel et al. (2012) Vitamin D deficiency, smoking, and lung function in the Normative Aging Study. Am J Respir Crit Care Med 186:616-21
Weuve, Jennifer; Glymour, M Maria; Hu, Howard et al. (2011) Forced expiratory volume in 1 second and cognitive aging in men. J Am Geriatr Soc 59:1283-92
Wilker, Elissa; Mittleman, Murray A; Litonjua, Augusto A et al. (2009) Postural changes in blood pressure associated with interactions between candidate genes for chronic respiratory diseases and exposure to particulate matter. Environ Health Perspect 117:935-40
Wilker, Elissa H; Alexeeff, Stacey E; Poon, Audrey et al. (2009) Candidate genes for respiratory disease associated with markers of inflammation and endothelial dysfunction in elderly men. Atherosclerosis 206:480-5
Litonjua, Augusto A (2008) Dietary factors and the development of asthma. Immunol Allergy Clin North Am 28:603-29, ix