Model of mucociliary clearance in cystic fibrosis lungs.

Research output: Contribution to journalArticle

  • External authors:
  • P Kurbatova
  • N Bessonov
  • V Volpert
  • H A W M Tiddens
  • C Cornu
  • P Nony
  • D Caudri
  • Agathe Bajard (Collaborator)
  • Yves Bertrand (Collaborator)
  • Frank Bretz (Collaborator)
  • Charlotte Castellan (Collaborator)
  • Sylvie Chabaud (Collaborator)
  • Catherine Cornu (Collaborator)
  • Frank Dufour (Collaborator)
  • Nathalie Eymard (Collaborator)
  • Roland Fisch (Collaborator)
  • Renzo Guerrini (Collaborator)
  • Behrouz Kassai (Collaborator)
  • Polina Kurbatova (Collaborator)
  • Salma Malik (Collaborator)
  • Patrice Nony (Collaborator)
  • David Pérol (Collaborator)
  • Gérard Pons (Collaborator)
  • Harm Tiddens (Collaborator)
  • Anna Rosati (Collaborator)
  • Corinne Alberti (Collaborator)
  • Catherine Chiron (Collaborator)
  • Rima Nabbout (Collaborator)
  • Vincent Jullien (Collaborator)
  • Pascal Benquet (Collaborator)
  • Fabrice Wendling (Collaborator)

Abstract

Mucus clearance is a primary innate defense mechanism in the human airways. Cystic fibrosis (CF) is a genetic disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. CF is characterized by dehydration of airway surface liquid and impaired mucociliary clearance. As a result, microorganisms are not efficiently removed from the airways, and patients experience chronic pulmonary infections and inflammation. We propose a new physiologically based mathematical model of muco-ciliary transport consisting of the two major components of the mucociliary clearance system: (i) periciliary liquid layer (PCL) and (ii) mucus layer. We study mucus clearance under normal conditions and in CF patients. Restoring impaired clearance of airway secretions in one of the major goals of therapy in patients with CF. We consider the action of the aerosolized and inhaled medication dornase alfa, which reduces the viscosity of cystic fibrosis mucus, by selectively cleaving the long DNA strands it contains. The results of the model simulations stress the potential relevance of the location of the drug deposition in the central or peripheral airways. Mucus clearance was increased in case the drug was primarily deposited peripherally, i.e. in the small airways.

Bibliographical metadata

Original languageEnglish
JournalJournal of Theoretical Biology
Volume372
DOIs
Publication statusPublished - 7 May 2015