title: Airway Surface Dehydration Aggravates Cigarette Smoke-Induced Hallmarks of COPD in Mice.
abstract: BACKGROUND
  Airway surface dehydration, caused by an imbalance between secretion and absorption of ions and fluid across the epithelium and/or increased epithelial mucin secretion, impairs mucociliary clearance. Recent evidence suggests that this mechanism may be implicated in chronic obstructive pulmonary disease (COPD). However, the role of airway surface dehydration in the pathogenesis of cigarette smoke (CS)-induced COPD remains unknown.
  
  
  OBJECTIVE
  We aimed to investigate in vivo the effect of airway surface dehydration on several CS-induced hallmarks of COPD in mice with airway-specific overexpression of the β-subunit of the epithelial Na⁺ channel (βENaC).
  
  
  METHODS
  βENaC-Tg mice and wild-type (WT) littermates were exposed to air or CS for 4 or 8 weeks. Pathological hallmarks of COPD, including goblet cell metaplasia, mucin expression, pulmonary inflammation, lymphoid follicles, emphysema and airway wall remodelling were determined and lung function was measured.
  
  
  RESULTS
  Airway surface dehydration in βENaC-Tg mice aggravated CS-induced airway inflammation, mucin expression and destruction of alveolar walls and accelerated the formation of pulmonary lymphoid follicles. Moreover, lung function measurements demonstrated an increased compliance and total lung capacity and a lower resistance and hysteresis in βENaC-Tg mice, compared to WT mice. CS exposure further altered lung function measurements.
  
  
  CONCLUSIONS
  We conclude that airway surface dehydration is a risk factor that aggravates CS-induced hallmarks of COPD.
authors.affiliation: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Leen J M
authors.initials: LJ
authors.lastname: Seys
authors.affiliation: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Fien M
authors.initials: FM
authors.lastname: Verhamme
authors.affiliation: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Dupont
authors.affiliation: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Elke
authors.initials: E
authors.lastname: Desauter
authors.affiliation: Department of Translational Pulmonology, Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Duerr
authors.affiliation: Department of Translational Pulmonology, Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany.
authors.forename: Ayca
authors.initials: A
authors.lastname: Seyhan Agircan
authors.affiliation: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Griet
authors.initials: G
authors.lastname: Conickx
authors.affiliation: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Guy F
authors.initials: GF
authors.lastname: Joos
authors.affiliation: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Guy G
authors.initials: GG
authors.lastname: Brusselle
authors.affiliation: Department of Translational Pulmonology, Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Mall
authors.affiliation: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Ken R
authors.initials: KR
authors.lastname: Bracke
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003681:Dehydration / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009077:Mucins / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000473:pathology*; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D012907:Smoking / Q000009:adverse effects; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D053503:Epithelial Sodium Channels; D009077:Mucins; D014028:Tobacco Smoke Pollution