INFLAMMATION, AUTONOMIC DYSFUNCTION AND AIRWAY DISEASE

中老年人支气管哮喘和慢性支气管炎的发病机制 老年人仍然模糊不清。 我们假设气道炎症 （继发于吸入特定过敏原和其他环境 代理商）和自主神经系统的功能失衡发挥 在这些疾病的特征性功能改变中的重要作用 （支气管扩张剂反应性增加， 非特异性支气管收缩刺激支气管粘液分泌过多）。 气道高反应性和/或粘液分泌过多可能尤其严重 可能发生在共存气道炎症的情况下， 神经调节紊乱 这项研究的目的是评估这一点， 假设在一个中年和老年男性的特点队列。 本研究将使用VA标准老化研究（NAS）人群， 由大约1800名居住在社区的男子组成， 每三年检查一次。 发生结果的数据 兴趣（对吸入异丙肾上腺素、乙酰甲胆碱 气道高反应性，报告的支气管粘液分泌过多）， 已经收集到了。 我们建议收集新的数据， 炎症指数（尿中的炎症介质）、自主神经 活动（尿儿茶酚胺排泄， 深呼吸）和自主反应性瞳孔α-肾上腺素能 和胆碱能反应）， 在1/2年的时间内进行检查。 拟议的研究将是第一个 对人口的调查，检查相互关系 炎症、自主活动和自主反应之间的关系， 探讨了炎症和自主神经系统 改变是发生气道高反应性所必需的 和粘液分泌过多。

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.