Nebulized Delivery of Albuterol during Exercise is Safe and Effective in Individuals with Cystic Fibrosis, but does not Augment Bronchodilation or Drug Delivery

Abstract

ObjectiveExercise is a cornerstone of therapeutic intervention for individuals with cystic fibrosis (CF). However, daily breathing treatments (e.g. chest physiotherapy and inhalation of nebulized albuterol) typically last ~90 minutes, providing a time‐barrier to completing daily exercise. Thus, the purpose of our study was to determine the effects of a combination therapy (exercise and nebulized albuterol) on airway function and bronchodilator delivery. We tested the hypotheses that combination therapy (exercise + nebulized albuterol) would 1) augment the bronchodilator effect compared to either intervention alone, and 2) increase the plasma concentration of albuterol compared to nebulized albuterol alone.MethodsParticipants with CF (n=9, 5 female, 25±2yrs, forced expiratory volume in 1 second (FEV1) =82±5%predicted) first completed a screening visit (V̇O2max test, cycle ergometer) and then three study visits in a randomized order. During each study visit, participants completed measures of airway function [FEV1 and forced expiratory flow from 25–75% of forced vital capacity (FEF25–75)], and a blood draw (n=8) to determine plasma albuterol concentration. Participants then completed one of three interventions [albuterol only, (A): 2.5mg nebulized albuterol over 15min; exercise only (E): 30min cycling exercise at 50% of peak watts; albuterol and exercise (A+E): 30min cycling exercise at 50% of peak watts with 2.5mg nebulized albuterol nebulized over the last 15min of cycling). Airway function and plasma albuterol were measured at 0, 15, 30, 45, 60, 90, 120, 180, and 240min after the intervention. Additional plasma albuterol measures were taken 5, and 6hrs post intervention. Data are mean±SD.ResultsDelivery of nebulized albuterol during exercise did not augment or prolong the bronchodilator effect compared to exercise or albuterol alone. The transient improvement in airway function during the interventions—increase in FEV1 (time=0.050, intervention p=0.166, interaction p=0.135) or increase in FEF25–75 (time p=0.001, intervention p=0.207, interaction p=0.990) — was not different between the three interventions. Delivery of nebulized albuterol during exercise did not increase the plasma concentration of albuterol compared to nebulized albuterol alone. The maximum plasma concentration of albuterol (Cmax) and the area under the curve (AUC) of albuterol concentration over time were not different between interventions (Cmax= 2.57±1.60 vs. 2.56±1.13ng·mL−1, p=0.982; AUC0–6hrs= 6.1±3.6 vs. 6.9±3.3hr·ng·mL−1, p=0.188; A vs. A+E interventions, respectively).ConclusionsDelivery of nebulized albuterol during moderate intensity exercise did not significantly alter bronchodilator effects or plasma levels of albuterol compared to albuterol or exercise alone. These data suggest that delivery of nebulized albuterol during exercise is safe and effective, but does not augment bronchodilator effects or drug delivery. This combination intervention (A+E) may be a time efficient method for individuals with cystic fibrosis to gain therapeutic effects of exercise and breathing treatments.Support or Funding InformationF32 HL131151, Cystic Fibrosis Research Inc.