Moderate intensity exercise mediates comparable increases in exhaled chloride as albuterol in individuals with cystic fibrosis

Abstract

Rationale Despite the demonstrated advantageous systemic changes in response to regular exercise for individuals with cystic fibrosis (CF), exercise is still viewed as an elective rather than a vital component of therapy, and it is likely that these benefits extend to and are partially mediated by exercise-induced changes in ion regulation. Objective We sought to determine if exercise could provide comparable improvements in ion regulation in the CF lung as albuterol, measured using exhaled breath condensate (EBC) collection and nasal potential difference (NPD). Methods Fourteen CF (13-42yrs.) and sixteen healthy (18-42yrs.) subjects completed a randomized crossover study of albuterol and submaximal exercise. EBC was collected at baseline, 30- and 60-min post-albuterol administration, and at baseline and during three separate 15 min cycling exercise bouts at low, moderate, and vigorous intensity (25, 50 and 65% of the maximum workload, respectively). NPD was performed at 30- and 80-min post albuterol or following moderate and vigorous intensity exercise. Results CF subjects had lower EBC Cl−, but no difference in EBC Na+ at baseline when compared to healthy subjects. EBC Cl− increased four-fold with moderate exercise which was similar to that seen 60-min post albuterol administration for CF subjects. Neither exercise nor albuterol altered EBC Na+. The change in NPD voltage with amiloride (ΔAmil) was greater and there was minimal Cl− secretion (ΔTCC) seen at baseline in the CF compared to the healthy subjects. ΔAmil was greater with both albuterol and exercise when compared to baseline within both CF and healthy groups, but there was no significant difference in the ΔTCC response with either treatment. Conclusion Both exercise and albuterol can alter ion regulation increasing Cl− secretion to a significant and similar degree in individuals with CF.

Effects of treadmill exercise versus Flutter® on respiratory flow and sputum properties in adults with cystic fibrosis: a randomised, controlled, cross-over trial

“…However, we found a significant reduction in sputum solids content in the five minutes following treadmill exercise but not after Flutter® therapy. Previously researchers have shown an inhibition of sodium conductance channels [11, 12, 37] and altered ion regulation with submaximal cycle exercise in adults with CF [13], suggesting improved airway hydration or airway surface liquid, however these changes only lasted for four minutes after ceasing exercise [37]. Our study provides some evidence to support the proposed increase in mucus water content with exercise in CF [10–12].…”

“…Airway clearance or physiotherapy techniques aim to improve mucus clearance by the following mechanisms: altering airflow (increasing the peak expiratory flow and creating an expiratory airflow bias, with the ratio of peak expiratory to peak inspiratory flow, PEF:PIF > 1.10); [6, 7] improving the physical properties of the mucus; [8] potentially increasing airway surface hydration; [9–13] and coughing [14]. …”

Exhaled Breath Condensate: Pilot Study of the Method and Initial Experience in Healthy Subjects

“…This observation is consistent with the hypothesis that EBC chloride correlates with plasma chloride levels (30). Physical exercise can alter ion regulation by increasing chloride secretion to a significant and similar degree compared to the individuals with cystic fibrosis (97). EBC of patients with chronic persistent cough is more acidic and has lower chloride levels than EBC of non-coughing healthy subjects (71).…”

TMEM16A Potentiation: A Novel Therapeutic Approach for the Treatment of Cystic Fibrosis

“…The use of P2Y2-receptor ligands in these studies is particularly relevant because the local release of ATP and UTP into the airway mucosa represents a key regulatory mechanism in the control of ion transport and fluid homeostasis (29,30) (Figure 4). The release of these mediators is a kinetic process that is stimulated by shear and compressive forces during normal breathing (26,34,35) and is proposed to adapt to maintain mucosal hydration as the respiration rate changes following the impaction of inhaled particulates on the epithelium and during cough (36,37). Tarran and colleagues (26) illustrated that imposing cyclical shear stress to CF-HBE cells to mimic tidal breathing induced an ATP-dependent increase in fluid secretion, measured as an increase in height of ASL.…”