title: A functional anatomic defect of the cystic fibrosis airway.
abstract: BACKGROUND
  The mechanisms underlying cystic fibrosis (CF) lung disease pathogenesis are unknown.
  
  
  OBJECTIVE
  To establish mechanisms linking anion transport with the functional microanatomy, we evaluated normal and CF piglet trachea as well as adult swine trachea in the presence of selective anion inhibitors.
  
  
  METHODS
  We investigated airway functional microanatomy using microoptical coherence tomography, a new imaging modality that concurrently quantifies multiple functional parameters of airway epithelium in a colocalized fashion.
  
  
  RESULTS
  Tracheal explants from wild-type swine demonstrated a direct link between periciliary liquid (PCL) hydration and mucociliary transport (MCT) rates, a relationship frequently invoked but never experimentally confirmed. However, in CF airways this relationship was completely disrupted, with greater PCL depths associated with slowest transport rates. This disrupted relationship was recapitulated by selectively inhibiting bicarbonate transport in vitro and ex vivo. CF mucus exhibited increased viscosity in situ due to the absence of bicarbonate transport, explaining defective MCT that occurs even in the presence of adequate PCL hydration.
  
  
  CONCLUSIONS
  An inherent defect in CF airway surface liquid contributes to delayed MCT beyond that caused by airway dehydration alone and identifies a fundamental mechanism underlying the pathogenesis of CF lung disease in the absence of antecedent infection or inflammation.
authors.affiliation: 1 Department of Medicine.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Birket
authors.forename: Kengyeh K
authors.initials: KK
authors.lastname: Chu
authors.forename: Linbo
authors.initials: L
authors.lastname: Liu
authors.forename: Grace H
authors.initials: GH
authors.lastname: Houser
authors.forename: Bradford J
authors.initials: BJ
authors.lastname: Diephuis
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Wilsterman
authors.forename: Gregory
authors.initials: G
authors.lastname: Dierksen
authors.forename: Marina
authors.initials: M
authors.lastname: Mazur
authors.forename: Suresh
authors.initials: S
authors.lastname: Shastry
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.forename: John D
authors.initials: JD
authors.lastname: Watson
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Smith
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Schuster
authors.forename: Justin
authors.initials: J
authors.lastname: Hanes
authors.forename: William E
authors.initials: WE
authors.lastname: Grizzle
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Sorscher
authors.forename: Guillermo J
authors.initials: GJ
authors.lastname: Tearney
authors.forename: Steven M
authors.initials: SM
authors.lastname: Rowe
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004848:Epithelium / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D009079:Mucociliary Clearance / Q000502:physiology; D013552:Swine; D041623:Tomography, Optical Coherence / Q000379:methods; D014132:Trachea / Q000473:pathology* / Q000503:physiopathology*
keywords: airway epithelium; cystic fibrosis; mucus transport; optical coherence tomography; viscosity