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.
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