Format

Send to

Choose Destination
Eur Respir J. 2019 Oct 31. pii: 1900419. doi: 10.1183/13993003.00419-2019. [Epub ahead of print]

Excess mucus viscosity and airway dehydration impact COPD airway clearance.

Author information

1
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
2
Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA.
3
Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA.
4
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
5
The Center for Nanomedicine at Wilmer Eye Institute, Johns Hopkins University, MD, USA.
6
Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA.
7
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA srrowe@uabmc.edu.

Abstract

The mechanisms by which cigarette smoking impairs airway mucus clearance are not well understood. We recently established a ferret model of cigarette smoke-induced chronic obstructive pulmonary disease (COPD) exhibiting chronic bronchitis. We investigated the effects of cigarette smoke on mucociliary transport (MCT).Adult ferrets were exposed to cigarette smoke for 6 months, with in vivo mucociliary clearance (MCC) measured by Tc-labeled DTPA (Tc-DTPA) retention. Excised tracheae were imaged with micro-optical coherence tomography. Mucus changes in primary human airway epithelial cells and ex vivo ferret airways were assessed by histology and particle tracking microrheology. Linear mixed models for repeated measures identified key determinants of MCT.Compared to air controls, cigarette smoke-exposed ferrets exhibited mucus hypersecretion, delayed MCC (-89.0%, p<0.01), and impaired tracheal MCT (-29.4%, p<0.05). Cholinergic stimulus augmented airway surface liquid (ASL) depth (5.8±0.3 to 7.3±0.6 µm, p<0.0001) and restored MCT (6.8±0.8 to 12.9±1.2 mm·min-1, p<0.0001). Mixed model analysis controlling for covariates indicated smoking exposure, mucus hydration (ASL) and CBF were important predictors of MCT. Ferret mucus was hyperviscous following smoke exposure in vivo or in vitro and contributed to diminished MCT. Primary cells from smokers with and without COPD recapitulated these findings, which persisted despite the absence of continued smoke exposure.Cigarette smoke impairs MCT by inducing airway dehydration and increased mucus viscosity, and can be partially abrogated by cholinergic secretion of fluid secretion. These data elucidate the detrimental effects of cigarette smoke exposure on mucus clearance and suggest additional avenues for therapeutic intervention.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center