Evaluating Non-ciliary Mechanisms of Airway Clearance in Muco-obstructive Lung Disease
University of North Carolina, Chapel Hill
Summary
Understanding mechanisms of mucus clearance from the airways may lead to treatments in muco-obstructive lung conditions. Mucociliary clearance (MCC) scans are a way to measure the rate at which a person's lungs can clear inhaled particles. Through a single-arm pilot study in participants with primary ciliary dyskinesia (PCD), the investigators will evaluate the effect of exercise as a way to increase clearance through a mechanism called gas liquid transport (GLT) where the faster flow of air through the lungs during exercise is able to clear more particles. The investigators will repeat MCC measures with exercise after administering hypertonic saline (HS) to evaluate the effects of mucus hydration on both GLT and cough clearance (CC). Aim 1. To quantify non-ciliary, non-cough mechanisms of mucus clearance (i.e., GLT) in PCD through an MCC protocol that introduces a standardized exercise intervention after isotope delivery. Aim 2. To evaluate whether exercise-induced GLT and/or CC are responsive to hydrator intervention, using a short acting bronchodilator with 7% HS prior to isotope delivery followed by MCC with exercise intervention.
Description
The investigators will perform an open label, single-arm interventional pilot study with all participants undergoing the interventions (exercise, and exercise with HS pretreatment) and serving as their own control to evaluate the effects of exercise on non-ciliary mucus clearance mechanisms in PCD to better identify role of GLT and CC. The investigators will also evaluate the effect of pretreatment with HS on GLT (if present) and CC, to determine if these mechanisms of mucus clearance are modifiable by future therapies in PCD and other muco-obstructive lung diseases. Patients will be asked to…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * 18 years old or older * Diagnosis of PCD with supporting genetics * Lung function with forced expiratory volume in 1 second (FEV1) percent predicted \>30% * Ability to exercise for 20 minutes (Exercise Assessment performed at screening visit) Exclusion Criteria: * Intolerance to 7% HS * Failure of HS tolerance test (HSTT) at visit 1 (V1), defined as a decline of 10% in FEV1 from baseline pre-bronchodilator (BD) FEV1 after 7% HS * Intolerance to levalbuterol * Exercise-induced asthma * Complex congenital heart disease or other exercise limitation * Lung transplantation…
Interventions
- BehavioralExercise
At either V2 or V3, after 16 minutes of baseline MCC data collection, participants will perform 20 minutes of moderate-intensity exercise based on the Borg Rating of Perceived Exertion (RPE) scale, on a cycle ergometer. The goal through this moderate intensity exercise is to increase respiratory rate and airflow velocity, thereby potentially inducing GLT. Participants will then resume MCC scan data collection post-exercise to continue to measure the effects induced by exercise on clearance from the lungs.
- OtherHS pretreatment with Exercise
At either V2 or V3, prior to the start of baseline MCC scanning, participants will undergo pretreatment with 4 puffs of inhaled levalbuterol (90 mcg per actuation, via spacer) followed by 4 ml of 7% HS via nebulizer. Participants will then start MCC scan data collection, and after 16 minutes of baseline MCC collection they will then complete 20 minutes of moderate intensity exercise according to the Borg RPE on a cycle ergometer. After 20 minutes, MCC scan will resume to continue to measure rates of clearance following HS pretreatment and exercise.
Location
- University of North Carolina at Chapel HillChapel Hill, North Carolina