title: Early cystic fibrosis lung disease: Role of airway surface dehydration and lessons from preventive rehydration therapies in mice.
abstract: Cystic fibrosis (CF) lung disease starts in the first months of life and remains one of the most common fatal hereditary diseases. Early therapeutic interventions may provide an opportunity to prevent irreversible lung damage and improve outcome. Airway surface dehydration is a key disease mechanism in CF, however, its role in the in vivo pathogenesis and as therapeutic target in early lung disease remains poorly understood. Mice with airway-specific overexpression of the epithelial Na(+) channel (βENaC-Tg) recapitulate airway surface dehydration and phenocopy CF lung disease. Recent studies in neonatal βENaC-Tg mice demonstrated that airway surface dehydration produces early mucus plugging in the absence of mucus hypersecretion, which triggers airway inflammation, promotes bacterial infection and causes early mortality. Preventive rehydration therapy with hypertonic saline or amiloride effectively reduced mucus plugging and mortality in neonatal βENaC-Tg mice. These results support clinical testing of preventive/early rehydration strategies in infants and young children with CF.
authors.affiliation: Department of Translational Pulmonology and Division of Pediatric Pulmonology & Allergy and Cystic Fibrosis Center, Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany. Electronic address: Marcus.Mall@med.uni-heidelberg.de.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Mall
authors.affiliation: Department of Translational Pulmonology and Division of Pediatric Pulmonology & Allergy and Cystic Fibrosis Center, Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany.
authors.forename: Simon Y
authors.initials: SY
authors.lastname: Graeber
authors.affiliation: Department of Translational Pulmonology and Division of Pediatric Pulmonology & Allergy and Cystic Fibrosis Center, Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Stahl
authors.affiliation: Department of Translational Pulmonology and Division of Pediatric Pulmonology & Allergy and Cystic Fibrosis Center, Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhou-Suckow
mesh_terms: D000818:Animals; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000473:pathology; D003681:Dehydration / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005440:Fluid Therapy / Q000379:methods*; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice
keywords: Airway surface dehydration; Cystic fibrosis; Early lung disease; Mouse model; Preventive therapy