Hypertonic Saline in Treatment of Pulmonary Disease in Cystic Fibrosis

Abstract

The pathogenesis of lung disease in cystic fibrosis is characterised by decreased airway surface liquid volume and subsequent failure of normal mucociliary clearance. Mucus within the cystic fibrosis airways is enriched in negatively charged matrices composed of DNA released from colonizing bacteria or inflammatory cells, as well as F-actin and elevated concentrations of anionic glycosaminoglycans. Therapies acting against airway mucus in cystic fibrosis include aerosolized hypertonic saline. It has been shown that hypertonic saline possesses mucolytic properties and aids mucociliary clearance by restoring the liquid layer lining the airways. However, recent clinical and bench-top studies are beginning to broaden our view on the beneficial effects of hypertonic saline, which now extend to include anti-infective as well as anti-inflammatory properties. This review aims to discuss the described therapeutic benefits of hypertonic saline and specifically to identify novel models of hypertonic saline action independent of airway hydration.

The effect of the decoy molecule PA401 on CXCL8 levels in bronchoalveolar lavage fluid of patients with cystic fibrosis

“…Nebulized HTS contributes to rehydration of the airways and increases mucociliary clearance, and additionally reduces chemokine levels in CF BALF via the disruption of ionic interactions with GAGs (Reeves et al, 2012;Reeves et al, 2011b). Results of the present study indicate that clinical application of a CXCL8 decoy may serve to decrease the inflammatory burden in the CF lung in vivo.…”

Hypertonic Saline Is Effective in the Prevention and Treatment of Mucus Obstruction, but Not Airway Inflammation, in Mice with Chronic Obstructive Lung Disease

“…Therapeutic strategies currently available in the clinic to clear mucus (i.e., "mucokinetic agents") are limited to hyperosmolar agents, such as inhaled hypertonic saline (HS) and mannitol. These agents, when inhaled, create osmotic gradients that draw water into the airway lumen and produce dose-dependent, transient improvements in airway surface liquid volume and mucociliary clearance (13)(14)(15)(16). In patients with CF, the prototypical osmolyte, HS, improved mucus clearance and lung function after short-term inhalation (17).…”

Defective goblet cell exocytosis contributes to murine cystic fibrosis–associated intestinal disease

“…In CF epithelia, a deficit in the capacity for salt and water secretion is intuitively associated with the production of mucus with altered rheological properties, i.e., dehydrated mucus. However, this hypothesis may not account fully for the pathology of CF mucoviscidosis based on several observations that include limited effectiveness of aerosolized hypertonic saline for CF lung clearance (5,6), failure of mucus release from CF mouse intestine bathed luminally with physiological Ringer's solutions (7), and mucus plugging of intestinal crypts in adult CF mice despite life-long osmotic laxative therapy (2).…”