Exercise Is Medicine in Cystic Fibrosis

Courtney M. Wheatley; Brad W. Wilkins; Eric M. Snyder


Exerc Sport Sci Rev. 2011;39(3):155-160. 

In This Article

Abstract and Introduction


Exercise activates adrenergic and purinergic pathways that regulate activity of ion channels on airway epithelia cells and sweat glands. Therefore, we hypothesize that exercise is not only an important therapy for cystic fibrosis (CF) patients by facilitating systemic improvements but, more importantly, that exercise can improve the pathophysiological ion dysregulation at a cellular level, thereby enhancing quality of life in CF.


Cystic fibrosis (CF) is one of the most common lethal genetic diseases in white patients, affecting nearly 30,000 individuals in the United States. Approximately 4% of white individuals carry one mutation of the CF transmembrane conductance regulator (CFTR) gene. The pathological consequences of this mutation can impinge function of the reproductive, digestive, and respiratory systems, as well as temperature regulation and fluid balance. Although CF is a multisystem disease, lung disease results in 85% of CF mortality, according to the CF Foundation Patient Registry. As an autosomal recessive disease, an individual with CF inherits a CFTR mutation on both their paternal and maternal alleles. Thus, the defective CFTR protein that is produced results in improper ion transport because of production of a nonfunctional or mislocalized CFTR chloride (Cl) channel on the apical membrane of epithelial cells. In the lung, this mutated CFTR leads to decreased Cl secretion and hyperabsorption of sodium (Na+) through epithelial Na+ channels (ENaC).[23] Consequently, in the CF lung, airway surface liquid (ASL) depth and mucociliary clearance are reduced, leading to airway obstruction, infection, and inflammation. Additionally, at the sweat gland, CFTR dysfunction leads to both high rates of sweat secretion and excessive loss of both Na+ and Cl. In contrast to the lungs, hypoabsorption of Na+ by ENaC in sweat gland ducts is linked to the lack of CFTR in plasma membranes. This altered sweat gland function can lead to dehydration, hyponatremia, and hypochloremia in patients with CF especially during exercise in the heat.[4,21,22]

Exercise can provide improvements to quality of life in CF patients, with benefits including increased exercise tolerance,[20] increased respiratory muscle endurance,[20] reduced residual volume,[3] increased sputum expectoration,[25] and reduced rate of decline in pulmonary function.[27] It also has been demonstrated that high levels of aerobic fitness in CF patients are associated with a significantly lower risk of death.[19] In addition, exercise training is known to improve fluid balance and retention of serum electrolytes in healthy individuals, likely through the plasma volume expansion that is characteristic of exercise and possibly through a direct effect on ion regulation in the sweat glands themselves. Therefore, exercise training has the potential to improve the fluid and salt loss due to sweat gland dysfunction in CF patients by reducing thermal strain and the incidence of dehydration, possibly through direct interaction of CFTR-related mechanisms. In this review, we will first present the previous work that has led to the belief that exercise is a vital component of the therapy regimen prescribed to CF patients because of the multitudinous systemic benefits. We will then present the emerging data and our recent research supporting the mechanisms by which exercise is medicine for CF patients at a cellular level by promoting improvements in ion balance by acting directly on sweat glands and airway epithelia to improve ion dysregulation and thereby enhance pulmonary function, quality of life, and life expectancy.


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