The pathogenesis of asthma and chronic bronchitis among middle-aged and older adults remains obscure. We hypothesize that both airway inflammation (secondary to inhalation of specific allergens and other environmental agents) and functional imbalance of the autonomic nervous system play important roles in functional alterations that characterize these diseases (increased bronchodilator responsiveness, increased responsiveness to nonspecific bronchoconstricting stimuli bronchial mucus hypersecretion). Airway hyperresponsiveness and/or mucus hypersecretion may be especially likely to occur in the setting of coexisting airway inflammation and disordered neural regulation. The goal of this study is to evaluate this hypothesis in a well-characterized cohort of middle-aged and elderly men. The study will use the VA Normative Aging Study (NAS) population which consists of approximately 1800 community-dwelling men who return for examination every three years. Data on the occurrence of outcomes of interest (heightened responsiveness to inhaled isoproterenol, methacholine airway hyperresponsiveness, reported bronchial mucus hypersecretion) are already being collected in this cohort. We propose collecting new data on indices of inflammation (inflammatory mediators in urine), autonomic activity (urinary catecholamine excretion, heart rate variations induced by deep breathing), and autonomic responsiveness pupillary alpha-adrenergic and cholinergic responses) from those NAS participants returning for examination over a 1/2 year period. The proposed study would be the first investigation of a human population which examines the interrelationships between inflammation, autonomic activity, and autonomic responsiveness, and explores the hypothesis that both inflammation and autonomic nervous system alterations are necessary for the occurrence of airway hyperresponsiveness and mucus hypersecretion.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL045089-01
Application #
3363982
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1990-07-01
Project End
1993-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
1
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
Kubzansky, L D; Sparrow, D; Vokonas, P et al. (2001) Is the glass half empty or half full? A prospective study of optimism and coronary heart disease in the normative aging study. Psychosom Med 63:910-6
Lazarus, R; Sparrow, D; Weiss, S T (1998) Impaired ventilatory function and elevated insulin levels in nondiabetic males: the Normative Aging Study. Eur Respir J 12:635-40
Kawachi, I; Sparrow, D; Kubzansky, L D et al. (1998) Prospective study of a self-report type A scale and risk of coronary heart disease: test of the MMPI-2 type A scale. Circulation 98:405-12
Lazarus, R; Sparrow, D; Weiss, S T (1998) Baseline ventilatory function predicts the development of higher levels of fasting insulin and fasting insulin resistance index: the Normative Aging Study. Eur Respir J 12:641-5
Kubzansky, L D; Kawachi, I; Weiss, S T et al. (1998) Anxiety and coronary heart disease: a synthesis of epidemiological, psychological, and experimental evidence. Ann Behav Med 20:47-58
Lazarus, R; Sparrow, D; Weiss, S (1998) Temporal relations between obesity and insulin: longitudinal data from the Normative Aging Study. Am J Epidemiol 147:173-9
Kubzansky, L D; Kawachi, I; Spiro 3rd, A et al. (1997) Is worrying bad for your heart? A prospective study of worry and coronary heart disease in the Normative Aging Study. Circulation 95:818-24
Sparrow, D; O'Connor, G T; Weiss, S T et al. (1997) Volume history effects and airway responsiveness in middle-aged and older men. The Normative Aging Study. Am J Respir Crit Care Med 155:888-92
Lazarus, R; Sparrow, D; Weiss, S T (1997) Alcohol intake and insulin levels. The Normative Aging Study. Am J Epidemiol 145:909-16
Lazarus, R; Sparrow, D; Weiss, S T (1997) Effects of obesity and fat distribution on ventilatory function: the normative aging study. Chest 111:891-8

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