Airway Protective Mechanisms in PD (R01)

Completed

Conditions: Parkinson Disease

Interventions: Drug: Capsaicin
Device: Resistive respiratory loads
Other: Event-related evoked potential using electroencephalography (EEG).
Procedure: Fluoroscopic swallow evaluation

Registration Number: NCT03321019

Lead Sponsor: University of Florida

Brief Summary: This study will collect data on various aspects of airway sensation and function, and determine how it relates to the development of swallowing and cough dysfunction in Parkinson's disease. Participants will be followed over a 3-year period, with once-per-year visits to collect the data.

Detailed Description: Aspiration pneumonia (APn) occurs at a disproportionately hig 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 the study team has 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.

The study team will accomplish these aims in 2 experimental studies. First, the study team will test the magnitude of respiratory resistive loads, in people with PD across a range of disease durations, and in a healthy control group. The study team will measure reflex cough, using a cough-inducing irritant (capsaicin), and swallowing function. The study team 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 the study team will perform electroencephalographic recordings time-locked to paired respiratory stimuli to determine cortical processing of airway sensory information. The study team 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 119

Inclusion Criteria

Between the ages of 45 and 85 years
Diagnosis of PD, Hoehn and Yahr stages I - IV, by a fellowship trained neurologist arriving at the diagnosis of PD by applying strict UK brain bank criteria (PD participants only)

Exclusion Criteria

Neurological disorders other than PD (i.e., stroke, etc.)
Difficulty complying due to neuropsychological dysfunction (i.e., severe depression)
Allergy to capsaicin or hot peppers
History of head or neck cancer
History of smoking in the past 5 years
Any neurological disorder including PD (Healthy control group only)

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Parkinson's disease	Fluoroscopic swallow evaluation	Men and women between the ages of 45 and 85 years with Parkinson's disease, and without any history of neurologic disorder/disease, head or neck cancer, or chronic respiratory illness.
Parkinson's disease	Resistive respiratory loads	Men and women between the ages of 45 and 85 years with Parkinson's disease, and without any history of neurologic disorder/disease, head or neck cancer, or chronic respiratory illness.
Healthy controls	Resistive respiratory loads	Men and women between the ages of 45 and 85 years without Parkinson's disease, or any history of neurologic disorder/disease, head or neck cancer, or chronic respiratory illness.
Parkinson's disease	Event-related evoked potential using electroencephalography (EEG).	Men and women between the ages of 45 and 85 years with Parkinson's disease, and without any history of neurologic disorder/disease, head or neck cancer, or chronic respiratory illness.
Healthy controls	Capsaicin	Men and women between the ages of 45 and 85 years without Parkinson's disease, or any history of neurologic disorder/disease, head or neck cancer, or chronic respiratory illness.
Healthy controls	Event-related evoked potential using electroencephalography (EEG).	Men and women between the ages of 45 and 85 years without Parkinson's disease, or any history of neurologic disorder/disease, head or neck cancer, or chronic respiratory illness.
Healthy controls	Fluoroscopic swallow evaluation	Men and women between the ages of 45 and 85 years without Parkinson's disease, or any history of neurologic disorder/disease, head or neck cancer, or chronic respiratory illness.
Parkinson's disease	Capsaicin	Men and women between the ages of 45 and 85 years with Parkinson's disease, and without any history of neurologic disorder/disease, head or neck cancer, or chronic respiratory illness.

Primary Outcome Measures

Name	Time	Method
Respiratory Sensitivity	3 years, three time points (assessed at year 1 visit, year 2 visit, and year 3 visit)	Slope of perception of resistive load and load resistance: Magnitude estimation of respiratory load (6 - no difficulty inhaling - 20 maximum difficulty inhaling) is plotted on the y-axis and respiratory load (0, 5, 10, 25 \& 40 cm H2O loads) is plotted on the x-axis. The slope of the resulting regression line is the measure.
Urge to Cough Sensitivity	3 years, three time points (assessed at year 1 visit, year 2 visit, and year 3 visit)	Urge to cough sensitivity slope: Slope of the line created by plotting the urge to cough (0 indicating none - 10 indicating maximal) on the y-axis and capsaicin concentration (increasing from 0, 25, 50, 100, 200 micromolar) on the x-axis.
Penetration-aspiration Scale	3 years, three time points (assessed at year 1 visit, year 2 visit, and year 3 visit)	Rating of airway intrusion of bolus material during swallowing ranging from 1 (best, no airway invasion) to 8 (worst, silent aspiration).

Secondary Outcome Measures

Name	Time	Method
Cough Peak Flow Rate	3 years, three time points (assessed at year 1 visit, year 2 visit, and year 3 visit)	Highest airflow rate (in liters per second; L/s) during cough
Swallowing Timing	3 years, three time points (assessed at year 1 visit, year 2 visit, and year 3 visit)	Duration from bolus head passing mandible to laryngeal vestibule closure measured in frames. Data are collected at 33 frames per second.