INFLAMMATION, AUTONOMIC DYSFUNCTION AND AIRWAY DISEASE

炎症、自主功能障碍和气道疾病

• 批准号: 3363982
• 负责人: DAVID W. SPARROW
• 金额: $ 14.5万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3363982
• 关键词: allergens; asthma; autonomic disorder; bronchial mucus; bronchoconstrictors; bronchodilators; case history; catecholamines; chromatography; electrocardiography; emphysema; heart rate; histamine; human middle age (35-64); human old age (65+); human subject; immunoglobulin E; inflammation; isoproterenol; leukotrienes; methacholine; neural information processing; parasympathetic nervous system; respiratory disorder diagnosis; respiratory disorder epidemiology; secretion; serotonin; sign /symptom; sympathetic nervous system; tobacco abuse; urinalysis

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.

中青年哮喘和慢性支气管炎的发病机制 老年人仍然默默无闻。 我们假设气道炎症 （继发于吸入特定过敏原和其他环境因素 剂）和自主神经系统功能失衡的发挥 在这些疾病特征的功能改变中发挥重要作用 （增加支气管扩张剂的反应性，增加对 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 可能发生在气道炎症共存的情况下 神经调节紊乱。 本研究的目的是评估这一点 这是在一组特征明确的中年和老年男性中提出的假设。 该研究将使用 VA 规范老龄化研究 (NAS) 人群 由大约 1800 名社区居民组成，他们返回 每三年进行一次考试。 有关结果发生的数据 兴趣（对吸入异丙肾上腺素、乙酰甲胆碱的反应性增强 气道高反应性，报道支气管粘液分泌过多） 已经被收集到这个队列中。 我们建议收集新数据 炎症指数（尿液中的炎症介质）、自主神经 活动（尿儿茶酚胺排泄、心率变化） 深呼吸）和自主反应性瞳孔α-肾上腺素能 和胆碱能反应）来自那些返回的 NAS 参与者 为期 1/2 年的检查。 拟议的研究将是第一个 对人群的调查，检查相互关系 炎症、自主活动和自主反应之间， 探索炎症和自主神经系统的假设 改变对于气道高反应性的发生是必要的 和粘液分泌过多。