TY - JOUR T1 - The mucus bundles responsible for airway cleaning are retained in cystic fibrosis and by cholinergic stimulation JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.00457-2018 VL - 52 IS - 2 SP - 1800457 AU - Anna Ermund AU - Lauren N. Meiss AU - Brendan Dolan AU - Andrea Bähr AU - Nikolai Klymiuk AU - Gunnar C. Hansson Y1 - 2018/08/01 UR - http://erj.ersjournals.com/content/52/2/1800457.abstract N2 - The beneficial effect of anticholinergic therapy for chronic lung diseases such as chronic obstructive pulmonary disease (COPD) is well documented, although cholinergic stimulation paradoxically inhibits liquid absorption, increases ciliary beat frequency and increases airway surface liquid transport.Using pig tracheobronchial explants, we quantified basal mucus transport before as well as after incubation with the clinically used antimuscarinic compound ipratropium bromide (Atrovent) and stimulation with acetylcholine.As expected, surface liquid transport was increased by acetylcholine and carbachol. In contrast, the mucus bundles secreted from the submucosal glands normally transported on the cilia were stopped from moving by acetylcholine, an effect inhibited by ipratropium bromide. Interestingly, in pigs lacking a functional cystic fibrosis (CF) transmembrane conductance regulator (CFTR) channel, the mucus bundles were almost immobile. As in wild-type pigs, CF surface liquid transport increased after carbachol stimulation. The stagnant CF mucus bundles were trapped on the tracheal surface attached to the surface goblet cells. Pseudomonas aeruginosa bacteria were moved by the mucus bundles in wild-type but not CF pigs.Acetylcholine thus uncouples airway surface liquid transport from transport of the surface mucus bundles as the bundles are dynamically inhibited by acetylcholine and the CFTR channel, explaining initiation of CF and COPD, and opening novel therapeutic windows.ACh uncouples airway surface liquid transport from transport of mucus bundles and lack of CFTR inhibits bundle movement http://ow.ly/Izbm30kb2F4 ER -