Mechanisms of airway protection dysfunction in Parkinson's disease

吸入性肺炎（APn）在帕金森病（PD）患者中的发生率不成比例地高 与年龄匹配的健康老年人进行比较。鉴于这一愿望， 肺炎感染是PD患者死亡的主要原因。APn的发生是多因素的 由于吞咽障碍（吞咽困难）而吸入物质而没有适当的咳嗽反应， 主要贡献因素。这些发现反映了吞咽和咳嗽都是感觉运动的事实 行为，并且因此需要对感觉刺激进行适当的检测和缩放，以便产生 适当的运动反应。本研究的长期目标是促进气道管理 神经退行性疾病患者的保护缺陷，以降低由于 吸入性肺部感染这方面的目标是，进一步 详细说明与气道保护障碍相关的感觉机制，以推进临床 管理这些病人。为了实现本申请的目的，我们确定了3个 目的：首先，确定呼吸道躯体感觉、反射性咳嗽与吞咽功能的关系 以及这些关系如何随着疾病进展而变化。第二、 确定感觉信息的皮层处理是否与反射性咳嗽的缺陷有关 第三，确定PD患者的中枢神经过滤如何影响PD患者的神经系统功能， 气道感觉刺激可能与气道保护性疾病的发展有关。我们将实现这些目标 在2项实验研究中。首先，我们将测试PD患者的呼吸阻力负荷的大小 在一系列疾病持续时间和健康对照组中。我们将测量反射性咳嗽，使用 引起咳嗽的刺激物（辣椒素）和吞咽功能。我们将在3个时间点进行这些检测， 间隔10-14个月，以确定呼吸感觉，咳嗽， 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的进展而变化。 接下来，我们将对成对的呼吸刺激进行脑电图记录，以确定 呼吸道感觉信息的皮层处理。我们将测量感觉的振幅和潜伏期 诱发电位峰值，并计算第一和第二配对刺激之间的峰值幅度的比率， 以确定感觉门控的程度。所提出的目标和研究的实现具有重要意义 因为这是我们研究计划中的必要一步， 识别，以及针对PD气道保护缺陷的靶向干预。完成这项研究 对于我们维持PD患者足够的气道保护功能的目标具有系统重要性; 预期结果将直接影响与气道相关的医疗保健费用、发病率和死亡率的降低。 保护赤字。

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.