A functional anatomic defect of the cystic fibrosis airway

Susan E. Birket, Kengyeh K. Chu, Linbo Liu, Grace H. Houser, Bradford J. Diephuis, Eric J. Wilsterman, Gregory Dierksen, Marina Mazur, Suresh Shastry, Yao Li, John D. Watson, Alexander T. Smith, Benjamin S. Schuster, Justin Hanes, William E. Grizzle, Eric J. Sorscher, Guillermo J. Tearney, Steven M. Rowe

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


Rationale: The mechanisms underlying cystic fibrosis (CF) lung disease pathogenesis are unknown. Objectives: 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. Measurements and Main 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.

Original languageEnglish (US)
Pages (from-to)421-432
Number of pages12
JournalAmerican journal of respiratory and critical care medicine
Issue number4
StatePublished - Aug 15 2014


  • Airway epithelium
  • Cystic fibrosis
  • Mucus transport
  • Optical coherence tomography
  • Viscosity

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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