Mechanisms of airway protection dysfunction in Parkinson's disease

帕金森病气道保护功能障碍的机制

• 批准号: 10213790
• 负责人: Karen W Hegland
• 金额: $ 30.1万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-09 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10213790
• 关键词: Address; Affective; Age; Aspiration Pneumonia; Behavior; Breathing; Capsaicin; Cause of Death; Clinical Management; Complex; Control Groups; Coughing; Data; Death Rate; Deglutition; Deglutition Disorders; Detection; Development; Diagnosis; Disease; Disease Progression; Effectiveness; Elderly; Esthesia; Etiology; Event; Evoked Potentials; Exhibits; Functional disorder; Gait; Goals; Health Care Costs; Hyporeflexia; Impairment; Infection; Intervention; Irritants; Knowledge; Lead; Lung infections; Measures; Mechanics; Mediating; Methods; Mission; Morbidity - disease rate; Motor; Nature; Neurodegenerative Disorders; Parkinson Disease; Participant; Patient Recruitments; Patients; Persons; Physiologic pulse; Procedures; Process; Public Health; Reflex action; Rehabilitation therapy; Research; Sensory; Specific qualifier value; Stimulus; Testing; Time; United States National Institutes of Health; advanced disease; base; cohort; disease diagnosis; experimental study; illness length; improved; injured airway; innovation; mortality; motor deficit; novel diagnostics; paired stimuli; posture instability; programs; protective behavior; relating to nervous system; respiratory; response; sensory gating; sensory mechanism; sensory stimulus; somatosensory

Aspiration pneumonia (APn) occurs at a disproportionately high rate in patients with Parkinson's disease (PD) versus healthy age-matched older adults. This is of particular public health concern given that aspiration pneumonia infection is a leading cause of death in persons with PD. The development of APn is multifactorial with aspiration of material from disordered swallowing (dysphagia) without proper cough response being the main contributing factor. These findings reflect the fact that both swallowing and cough are sensorimotor behaviors, and thus require appropriate detection and scaling of a sensory stimulus in order to produce an appropriate motor response. The long-term goal of this research is to advance the management of airway protection deficits in patients with neurodegenerative disease in order to decrease morbidity and mortality due to aspiration related lung infection. The objective here, which is a critical step in pursuit of that goal, is to further specify the sensory mechanisms associated with airway protection disorders in order to advance the clinical management of these patients. In order to accomplish the objective of this application we have identified 3 aims: First, determine relationship(s) between airway somatosensation, reflex cough and swallowing function in people with PD, and how these relationships may change with disease progression, over time. Second, determine whether cortical processing of sensory information is associated with deficits in reflex cough sensitivity or swallowing function in people with PD, and third, to determine how the central neural filtering of airway sensory stimuli may relate to the development of airway protective disorders. We will accomplish these aims in 2 experimental studies. First, we will test the magnitude of respiratory resistive loads, in people with PD across a range of disease durations, and in a healthy control group. We will measure reflex cough, using a cough-inducing irritant (capsaicin), and swallowing function. We will perform these tests at 3 time-points, spaced 10-14 months apart, in order to determine the relationships between respiratory sensation, cough sensitivity and effectiveness, and swallowing function, and how they change with advancing disease duration. Next we will perform electroencephalographic recordings time-locked to paired respiratory stimuli to determine cortical processing of airway sensory information. We will measure the amplitude and latency of the sensory evoked potential peaks, and compute ratios of peak amplitude between the first and second paired stimulus in order to determine the degree of sensory gating. The realization of the proposed aims and studies is significant because it is a necessary step in our program of research that is expected to lead to earlier, more accurate identification, as well as targeted interventions for airway protection deficits in PD. Completion of this research is systematically important for our goal of maintaining adequate airway protective function in PD patients; the results are expected to directly impact reductions in health care costs, morbidity, and mortality related to airway protection deficits.

帕金森氏病（PD）患者的抽吸肺炎（APN）以不成比例的速度发生。 相对于健康年龄匹配的老年人。鉴于愿望，这特别是公共卫生的关注 肺炎感染是PD患者死亡的主要原因。 APN的开发是多因素的 吞咽无序（吞咽困难）没有适当咳嗽反应的材料吸入 主要促成因素。这些发现反映了吞咽和咳嗽都是感觉运动的事实 行为，因此需要对感觉刺激的适当检测和缩放，以产生 适当的电动机响应。这项研究的长期目标是提高气道管理 神经退行性疾病患者的保护缺陷，以降低应有的发病率和死亡率 与抽吸有关的肺部感染。这里的目标是追求该目标的关键一步，是进一步 指定与气道保护障碍相关的感官机制以推进临床 这些患者的管理。为了实现此应用程序的目标，我们已经确定了3 目的：首先，确定气道节交，反射咳嗽和吞咽功能之间的关系 随着时间的流逝，在患有PD的人以及这些关系如何随疾病进展而变化。第二， 确定感觉信息的皮质处理是否与反射咳嗽中的缺陷有关 PD患者的灵敏度或吞咽功能，第三名，以确定中央神经过滤的方式 气道感觉刺激可能与气道保护障碍的发展有关。我们将完成这些 在两项实验研究中的目标。首先，我们将在患有PD的人中测试呼吸电阻载荷的大小 在一系列疾病持续时间内以及健康对照组。我们将使用一个 咳嗽引起刺激性（辣椒素）和吞咽功能。我们将以3个时间点执行这些测试， 间隔10-14个月，以确定呼吸感觉之间的关系 敏感性和有效性，吞咽功能，以及它们如何随着疾病持续时间而变化。 接地 气道感觉信息的皮质处理。我们将测量感觉的幅度和潜伏期 诱发电势峰以及第一和第二对刺激之间的峰值幅度的计算比率 为了确定感觉门的程度。所提出的目的和研究的实现非常重要 因为这是我们的研究计划中必不可少的一步，预计将导致更早，更准确 识别以及PD中气道保护缺陷的有针对性干预措施。完成这项研究 对于我们在PD患者中维持足够的气道保护功能的目标在系统上很重要；这 预计结果将直接影响与气道相关的医疗保健成本，发病率和死亡率的降低 保护缺陷。

项目成果

Primary site of constriction during the compression phase of cough in healthy young adults.

健康年轻人咳嗽受压阶段的主要收缩部位。

• DOI: 10.1016/j.resp.2023.104033
• 发表时间: 2023
• 期刊: Respiratory physiology & neurobiology
• 影响因子: 2.3
• 作者: Kim,JaYoung;Davenport,PaulW;Mou,Yuhan;Hegland,Karen
• 通讯作者: Hegland,Karen

A comprehensive review of the diagnosis and treatment of Parkinson's disease dysphagia and aspiration.

• DOI: 10.1080/17474124.2020.1769475
• 发表时间: 2020-06
• 期刊: EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY
• 影响因子: 3.9
• 作者: Patel, Bhavana;Legacy, Joseph;Hegland, Karen W.;Okun, Michael S.;Herndon, Nicole E.
• 通讯作者: Herndon, Nicole E.