title: Hypertonic saline is effective in the prevention and treatment of mucus obstruction, but not airway inflammation, in mice with chronic obstructive lung disease.
abstract: Recent evidence suggests that inadequate hydration of airway surfaces is a common mechanism in the pathogenesis of airway mucus obstruction. Inhaled hypertonic saline (HS) induces osmotic water flux, improving hydration of airway surfaces. However, trials in patients with obstructive lung diseases are limited. The aim of this study was to investigate effects of HS on mucus obstruction and airway inflammation in the prevention and treatment of obstructive lung disease in vivo. We, therefore, used the β-epithelial Na(+) channel (βENaC)-overexpressing mouse as a model of chronic obstructive lung disease and determined effects of preventive and late therapy with 3% HS and 7% HS on pulmonary mortality, airway mucus obstruction, and inflammation. We found that preventive treatment with 3% HS and 7% HS improved growth, reduced mortality, and reduced mucus obstruction in neonatal βENaC-overexpressing mice. In adult βENaC-overexpressing mice with chronic lung disease, mucus obstruction was significantly reduced by 7% HS, but not by 3% HS. Treatment with HS triggered airway inflammation with elevated keratinocyte chemoattractant levels and neutrophils in airways from wild-type mice, but reduced keratinocyte chemoattractant in chronic neutrophilic inflammation in adult βENaC-overexpressing mice. Our data demonstrate that airway surface rehydration with HS provides an effective preventive and late therapy of mucus obstruction with no consistent effects on inflammation in chronic lung disease. These results suggest that, through mucokinetic effects, HS may be beneficial for patients with a spectrum of obstructive lung diseases, and that additional strategies are required for effective treatment of associated airway inflammation.
authors.affiliation: Department of Translational Pulmonology, Translational Lung Research Center, University of Heidelberg, Im Neuenheimer Feld 350, Heidelberg, Germany.
authors.forename: Simon Y
authors.initials: SY
authors.lastname: Graeber
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhou-Suckow
authors.forename: Jolanthe
authors.initials: J
authors.lastname: Schatterny
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hirtz
authors.forename: Richard C
authors.initials: RC
authors.lastname: Boucher
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Mall
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002633:Chemotaxis / Q000187:drug effects; D004195:Disease Models, Animal; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D007249:Inflammation; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051379:Mice; D009093:Mucus / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*
chemical_list: D053503:Epithelial Sodium Channels; D012462:Saline Solution, Hypertonic; C507049:Scnn1b protein, mouse