High salt or low volume: A critical dissection of a mechanistic controversy in cystic fibrosis.

摘要

Cystic fibrosis is an autosomal recessive disease caused by a mutation in the sequence coding for a transmembrane chloride channel called the cystic fibrosis transmembrane conductance regular (CFTR). Complications due to chronic lung infections are the primary cause of the decreased quality of life and the leading cause of mortality seen in cystic fibrosis patients. Two main hypotheses for the origin and mechanism of bacterial colonization of cystic fibrosis lungs exist and have been debated for years. The high salt hypothesis equates the colonization of the lungs to an increased concentration of sodium and chloride in the layer of liquid covering the surface of the lungs, known as airway surface liquid (ASL), inhibits the bactericidal activity of airway defensins. The low volume hypothesis suggests that the decreased volume of the ASL, as a result of increased sodium absorption causes the cilia to collapse in the absence of a liquid covering thereby halting mucus clearance. An analysis of available data for sodium and chloride concentrations in liquid lining of lungs and the depth was conducted using an independent samples student's t-test. The evidence evaluated supports that no difference exists between the liquid lining of the normal and cystic fibrosis lungs for salt concentrations (Sodium: p = 0.316, Chloride: p = 0.30) or depth (p = 0.16). The findings of this study suggest an alternative mechanism for initial bacterial colonization of the lungs in cystic fibrosis.