Mechanisms of airway protection dysfunction in Parkinson's disease

吸入性肺炎(APN)在帕金森病(PD)患者中的发生率高得不成比例 与健康的年龄匹配的老年人的对比。考虑到这一愿望，这是特别令人担忧的公共卫生问题 肺炎感染是帕金森病患者死亡的主要原因。APN的发展是多因素的 从无序吞咽(吞咽困难)中吸入物质而没有适当的咳嗽反应是 主要影响因素。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进行适当的检测和缩放，以便产生 适当的运动反应。这项研究的长期目标是推进呼吸道管理 神经退行性疾病患者的保护缺陷，以降低发病率和死亡率 与吸入相关的肺部感染有关。这里目标是为实现这一目标迈出的关键一步，目的是进一步 明确与呼吸道保护障碍相关的感觉机制，以促进临床 这些病人的管理。为了实现本应用程序的目标，我们确定了3个 目的：首先，确定呼吸道体感、反射性咳嗽和吞咽功能之间的关系(S) 在帕金森病患者中，以及随着时间的推移，这些关系可能如何随着疾病的进展而改变。第二, 确定感觉信息的皮质处理是否与反射性咳嗽的缺陷有关 帕金森病患者的敏感度或吞咽功能，以及第三，确定中枢神经过滤如何 呼吸道感觉刺激可能与呼吸道保护性疾病的发生有关。我们将实现这些目标 旨在进行2项实验研究。首先，我们将测试帕金森病患者的呼吸阻力负荷的大小 在一系列病程中，并在健康对照组中。我们将使用一种 具有止咳、刺激性(辣椒素)、吞咽功能。我们将在3个时间点进行这些测试， 间隔10-14个月，以确定呼吸感、咳嗽 敏感度和有效性，吞咽功能，以及它们如何随着病程的进展而变化。 接下来，我们将对配对的呼吸刺激进行时间锁定的脑电记录，以确定 呼吸道感觉信息的皮质处理。我们将测量感官的幅度和潜伏期 诱发电位峰值，并计算第一对刺激与第二对刺激之间的峰值幅度比 以确定感觉门控的程度。实现拟议的目标和研究具有重要意义。 因为这是我们研究计划中的必要步骤，预计将导致更早、更准确的结果 对帕金森病患者的呼吸道保护缺陷进行有针对性的识别和干预。完成这项研究 对于我们在PD患者中维持足够的呼吸道保护功能的目标是系统地重要的； 预计结果将直接影响与呼吸道相关的医疗费用、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.