Dynamic Respiratory Muscle Function in Late-Onset Pompe Disease

Completed

Conditions: Pompe Disease

Registration Number: NCT02354664

Lead Sponsor: University of Florida

Brief Summary: This study intends to evaluate dynamic respiratory motor performance as a valuable measure of pulmonary function in adults with late-onset Pompe disease. The investigators will adopt a strategy that includes comprehensive evaluations of respiratory volume, flow, and timing parameters during resting and loaded breathing. These evaluations will then be associated to the standard clinical measure of maximal inspiratory pressure, the static inspiratory muscle function, as well as magnetic resonance imaging of thoracic expansion and diaphragmatic descent at rest and with exertion. Outcomes in participants with late-onset Pompe disease will be contrasted to the function of age- and gender-matched control subjects. This approach will enable the investigators to evaluate the relationship between dynamic diaphragmatic function and respiratory motor function.

Detailed Description: The following tests will be completed over a two-day period: Respiratory pressure tests, breathing test, magnetic resonance imaging and magnetic resonance spectroscopy (MRI and MRS).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 14

Inclusion Criteria

Confirmed diagnosis of Pompe disease OR
Be an age and gender-matched unaffected control subject

Exclusion Criteria

Pre-existing obstructive lung disease or asthma
Forced vital capacity (FVC) <30% or >80% of age/gender predicted values
Inability to travel to the study site
Requirement for positive pressure ventilator support when awake and upright
Participation in longitudinal studies that may independently alter lung function
Presence of any other chronic medical condition that, in the opinion of the investigator, would make the subject unsuitable for the study

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Inspiratory Load Compensation - Inspiratory Volume	Day 1	For ILC testing, a commercially available, spring-loaded device provided a pressure load to inspiration that is independent of inspiratory flow. The patient had to generate enough threshold inspiratory pressure in order to receive airflow. The tension of the spring was adjusted to regulate the threshold pressure of the imposed load. Volume, flow and timing responses were evaluated to an inspiratory threshold load equivalent to 40% of PImax.
Respiratory Muscle Endurance Task	Day 2	Endurance was evaluated by identifying the time limit (Tlim) that a participant could maintain ventilation while breathing with a submaximal inspiratory threshold load. The test begin after a one-hour rest. After reaching a steady state breathing pattern (e.g. stable tidal volumes for \>30 seconds), a threshold inspiratory load equivalent to 40% of PIMAX was placed on the inspiratory port of the mouthpiece. During the loaded breathing condition, the respiratory rate was set to each subject's self-selected resting breathing rate. The perceived exertion was monitored, and subjects received encouragement to maintain the target rate and mouth pressure. Encouragement was provided to maintain the established breathing pattern and to continue to task failure. The test ended when the subject could not open the threshold valve for three consecutive breaths.
Inspiratory Load Compensation - Inspiratory Flow	Day 1	For ILC testing, a commercially available, spring-loaded device provided a pressure load to inspiration that is independent of inspiratory flow. The patient had to generate enough threshold inspiratory pressure in order to receive airflow. The tension of the spring was adjusted to regulate the threshold pressure of the imposed load. Volume, flow and timing responses were evaluated to an inspiratory threshold load equivalent to 40% of PImax.
Inspiratory Load Compensation - Inspiratory Time	Day 1	For ILC testing, a commercially available, spring-loaded device provided a pressure load to inspiration that is independent of inspiratory flow. The patient had to generate enough threshold inspiratory pressure in order to receive airflow. The tension of the spring was adjusted to regulate the threshold pressure of the imposed load. Volume, flow and timing responses were evaluated to an inspiratory threshold load equivalent to 40% of PImax.

Secondary Outcome Measures

Name	Time	Method
Thoracic MRI	Day 1	Chest wall and diaphragmatic motions was measured in three planes with dynamic magnetic resonance imaging (MRI). The cradio-caudal change in diaphragm excursion between full inspiration and full expiration (representing diaphragm descent) was measured in the frontal plane. The anterior-posterior change in the area of the right and left sides of the chest cavity was measured in the sagittal plane (representing chest expansion). Diaphragm and chest excursion was recorded dynamically during 30-second periods of resting breathing and deep breathing.