RT Journal Article
SR Electronic
T1 Pathological mucus and impaired mucus clearance in cystic fibrosis patients result from increased concentration, not altered pH
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1801297
DO 10.1183/13993003.01297-2018
VO 52
IS 6
A1 David B. Hill
A1 Robert F. Long
A1 William J. Kissner
A1 Eyad Atieh
A1 Ian C. Garbarine
A1 Matthew R. Markovetz
A1 Nicholas C. Fontana
A1 Matthew Christy
A1 Mehdi Habibpour
A1 Robert Tarran
A1 M. Gregory Forest
A1 Richard C. Boucher
A1 Brian Button
YR 2018
UL http://erj.ersjournals.com/content/52/6/1801297.abstract
AB Cystic fibrosis (CF) is a recessive genetic disease that is characterised by airway mucus plugging and reduced mucus clearance. There are currently alternative hypotheses that attempt to describe the abnormally viscous and elastic mucus that is a hallmark of CF airways disease, including: 1) loss of CF transmembrane regulator (CFTR)-dependent airway surface volume (water) secretion, producing mucus hyperconcentration-dependent increased viscosity, and 2) impaired bicarbonate secretion by CFTR, producing acidification of airway surfaces and increased mucus viscosity.A series of experiments was conducted to determine the contributions of mucus concentration versus pH to the rheological properties of airway mucus across length scales from the nanoscopic to macroscopic.For length scales greater than the nanoscopic, i.e. those relevant to mucociliary clearance, the effect of mucus concentration dominated over the effect of airway acidification.Mucus hydration and chemical reduction of disulfide bonds that connect mucin monomers are more promising therapeutic approaches than alkalisation.Over length scales greater than the mesh size of the mucin polymeric network of mucus, concentration, and not pH, dominates the physical properties of mucus that are associated with cystic fibrosis airways disease http://ow.ly/K92u30m2RDC