The goal of this application is to determine if the administration of nebulized albuterol during exercise can improve the delivery and physiological responses of albuterol, a bronchodilator, in individuals with cystic fibrosis (CF). This project wil provide excellent intellectual and robust technical training opportunities to support the applicant in achieving her goal of becoming an independent investigator studying translational cardiopulmonary physiology.
Specific Aim 1 will test the hypothesis that the degree of bronchodilation will be greatest when exercise and albuterol are combined in healthy individuals and in those with CF, compared to albuterol or exercise alone. We will assess bronchodilation [change in forced expiratory volume in 1 second (FEV1), and forced expiratory flow for 25-75% of the forced vital capacity (FEF25-75)] in response to three treatments: 1) exercise, 2) nebulized albuterol administration, and 3) exercise combined with albuterol administration.
In Specific Aim 2, we will test the hypothesis that the duration of bronchodilation will be lowest after exercise, and will significantly increase when exercise is combined with albuterol. We will assess bronchodilation for 6 hours after each treatment and will accept our hypothesis if albuterol administration during moderate aerobic exercise has the largest area under the curve for bronchodilation (FEV1 and FEF25-75) over 6 hours.
Specific Aim 3 will test the hypothesis that giving nebulized albuterol during exercise will improve drug delivery. We will measure plasma albuterol concentrations for 6 hours in response to each of the three conditions and run pharmacokinetic analyses. We predict that the delivery of nebulized albuterol during exercise will have an improved pharmacokinetic profile (maximum concentration and area under the curve) as compared to standard nebulized albuterol therapy. Administration of an inhaled bronchodilator during exercise may lead to better delivery and distribution of the drug, which could augment or prolong the bronchodilatory and pharmacokinetic effect of exercise or albuterol alone. This study will serve as proof of concept that combining exercise with aerosolized drug administration can improve drug delivery, which would be beneficial for other inhaled therapies in CF. In addition, regular delivery of albuterol during exercise would replace a daily sedentary activity with an active one, which could help CF patients reap the many benefits of regular exercise by allowing two therapies (exercise and inhaled medications) to be utilized at the same time while potentially receiving synergistic treatment effects. We propose a novel, high-impact, and translational study investigating the pharmacokinetic and bronchodilatory effects of delivering nebulized albuterol during exercise. The research team, combined with the extensive resources at the Mayo Clinic, provides the optimal training environment to complete studies in this area.
Individuals with cystic fibrosis can spend upward of 90 minutes a day taking inhaled medications, including albuterol, which is used to open their airways. The proposed project will determine if taking albuterol during exercise, which also opens the airways, can help to further open the airways and improve the delivery of the drug. In addition to improving the delivery of the drug, if completed regularly, taking albuterol during exercise would turn sedentary time into active time and help patients with cystic fibrosis gain the many benefits of regular exercise. If successful, this study would be the first step toward utilizig this method of drug delivery with other inhaled medications and in other clinical populations who regularly use inhaled medications.
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