Abstract
Cystic fibrosis (CF) is caused by a defect in the CF transmembrane regulator that leads to depletion and dehydration of the airway surface liquid (ASL) of the lung epithelium, providing an environment that can be infected by bacteria leading to increased morbidity and mortality. Pseudomonas aeruginosa chronically infects more than 80% of CF patients and one hallmark of infection is the emergence of a mucoid phenotype associated with a worsening prognosis and more rapid decline in lung function. Hypertonic saline (HS) is a clinically proven treatment that improves mucociliary clearance through partial rehydration of the ASL of the lung. Strikingly, while HS therapy does not alter the prevalence of P. aeruginosa in the CF lung it does decrease the frequency of episodes of acute, severe illness known as infective exacerbations among CF patients. In this article, we propose a hypothesis whereby the positive clinical effects of HS treatment are explained by the osmotic sensitivity of the mucoid sub-population of P. aeruginosa in the CF lung leading to selection against this group in favor of the osmotically resistant non-mucoid variants.
Highlights
In this paper we will discuss the background to the use of hypertonic saline (HS) in the treatment of cystic fibrosis (CF) and propose a hypothesis whereby the positive effects of this approach can be explained by population shifts of Pseudomonas aeruginosa, the major chronic infecting bacterium of the CF lung.Cystic Fibrosis and Chronic Pseudomonas aeruginosa Infection Cystic fibrosis is an inherited condition that results from mutations in the gene encoding the CF transmembrane regulator (CFTR), a cAMP-regulated chloride channel in epithelial tissues
We propose a hypothesis whereby the positive clinical effects of HS treatment are explained by the osmotic sensitivity of the mucoid sub-population of P. aeruginosa in the CF lung leading to selection against this group in favor of the osmotically resistant nonmucoid variants
As more than 80% of adult CF patients have mucoid P. aeruginosa, mucoid biofilms may act as a reservoir for the infection of previously healthy parts of the lung through biofilm dispersal mechanisms that lead to the release of motile, non-mucoid bacteria (VanDevanter and Van Dalfsen, 2005; Kirov et al, 2007; Bjarnsholt et al, 2010), this proposal has been challenged (Reid et al, 2006) and mucoid variants have been shown to be seeding dispersal proficient (Kirov et al, 2007)
Summary
In this paper we will discuss the background to the use of hypertonic saline (HS) in the treatment of cystic fibrosis (CF) and propose a hypothesis whereby the positive effects of this approach can be explained by population shifts of Pseudomonas aeruginosa, the major chronic infecting bacterium of the CF lung.Cystic Fibrosis and Chronic Pseudomonas aeruginosa Infection Cystic fibrosis is an inherited condition that results from mutations in the gene encoding the CF transmembrane regulator (CFTR), a cAMP-regulated chloride channel in epithelial tissues. We propose a hypothesis whereby the positive clinical effects of HS treatment are explained by the osmotic sensitivity of the mucoid sub-population of P. aeruginosa in the CF lung leading to selection against this group in favor of the osmotically resistant nonmucoid variants.
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