Influence of Exercise on Airway Epithelia in Cystic Fibrosis

Abstract

Regular exercise is recommended as part of cystic fibrosis (CF) physiotherapy. Exercise delays the development of pulmonary disease in CF patients; however, the cellular mechanisms responsible for these improvements are unclear. This review expands on the hypothesis that exercise improves CF pathophysiological ion dysregulation via purinergic and adrenergic pathways by describing the effects of 5' adenosine monophosphate-activated protein kinase (AMPK), atrial natriuretic peptide (ANP), and arginine-vasopressin (AVP) on CF airway epithelia. Activation of AMPK decreases Na(+) absorption, increases airway surface liquid, and reduces oxidative stress and inflammation. Plasma ANP inhibits the basolateral Na(+)/K(+)-ATPase and may therefore reduce epithelial water absorption. Airway epithelia respond to plasma AVP and secrete AVP in response to elevated bradykinin. AVP stimulates the basolateral Na(+)/K(+)/2Cl(-) exchanger, thereby increasing Cl(-) secretion, reducing Na(+) absorption, and promoting basolateral to luminal water flux. In addition, AVP may increase cilia beat frequency in airway epithelia via a Ca(2+)-dependent mechanism. This review will describe the effects of exercise on AMPK activation, ANP release, and AVP secretion; we hypothesize that the mechanical and metabolic perturbations that occur with exercise may be beneficial in preventing CF lung pathogenesis by improving airway hydration, mucociliary clearance, and reducing markers of inflammation.

Rehabilitation in Patients with Chronic Respiratory Disease Other than Chronic Obstructive Pulmonary Disease: Exercise and Physical Activity Interventions in Cystic Fibrosis and Non-Cystic Fibrosis Bronchiectasis

“…However, the amount of evidence supporting this hypothesis is still very limited. Third, exercise possibly improves pathophysiological ion dysregulation via adrenergic and purinergic pathways [92]. …”

Aerobic exercise and respiratory muscle strength in patients with cystic fibrosis

“…6 A single exercise bout resulted in inhibition of epithelial sodium channels in patients with CF partially normalizing transepithelial potential difference, 7 while progressive aerobic exercise resulted in increased recruitment in lung ventilation. 8 Following a supervised threemonth running conditioning program, CF patients exhibited increased ventilatory muscle endurance. 9 CF patients subjected to high intensity exercise training did not develop overt low frequency fatigue of the respiratory muscles.…”

Parent and Child Perceptions of a Self-Regulated, Home-Based Exercise Program for Children With Cystic Fibrosis

“…Within the past two decades, exercise has been added to the complement of recommended treatments for CF (Dwyer, Elkins, & Bye, 2011; Higgins et al, 2013). Exercise can be both physiologically and psychologically advantageous with specific benefits that relate to lung health, including enhanced sputum clearance (Cholewa & Paolone, 2012), reduced breathlessness (Moorcroft, Dodd, Morris, & Webb, 2004), preserved and possibly improved lung function (Paranjape et al, 2012), and possibly even lower mortality (van de Weert-van Leuuwen et al, 2012). …”