Rationale for hypertonic saline therapy for cystic fibrosis lung disease.
Cystic fibrosis (CF) is caused by alterations in the CF transmembrane conductance regulator ( CFTCR) gene. More than 1400 mutations in the CFTCR gene have been described, but the most common mutation (noted in 70% of CF chromosomes) is DeltaF508. Alterations in the CFTCR gene result in deranged sodium and chloride ion transport channels. This leads to failure of airway epithelia to hydrate their surfaces normally, particularly in response to infectious or toxic insults. Additional effects include mucus adhesion to airway surface, chronic inflammation, and infections. The concept that airway surface dehydration can cause CF-like lung disease is supported by in vitro data and in vivo animal models. Rehydrating airway surfaces may reduce or prevent lung injury and damage. Short- and longer term studies have shown that inhalation of hypertonic saline is well tolerated and improves lung function, reduces exacerbations, and improves quality of life in CF patients. This review discusses the importance of airway epithelial sodium and chloride channels in the pathogenesis of CF, and strategies (particularly the use of inhaled hypertonic saline) to reverse or minimize lung inflammation and injury in this disease.
Tarran
Robert
R
Cystic Fibrosis/Pulmonary Research and Treatment Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7248, USA.
Donaldson
Scott
S
Boucher
Richard C
RC
D000280:Administration, Inhalation; D000336:Aerosols; D001693:Biological Transport, Active; D002463:Cell Membrane Permeability; D003550:Cystic Fibrosis / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009079:Mucociliary Clearance; D020545:Respiratory Mucosa / Q000503:physiopathology; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage* / Q000494:pharmacology
D000336:Aerosols; D053503:Epithelial Sodium Channels; D012462:Saline Solution, Hypertonic; D019005:Cystic Fibrosis Transmembrane Conductance Regulator