MINI-SYMPOSIUM: MUCUS
Airway mucus in cystic fibrosis

https://doi.org/10.1016/S1526-0550(02)00005-7Get rights and content

Abstract

Defective expression and function of the cystic fibrosis transmembrane conductance regulator (CFTR) in cystic fibrosis (CF) airway epithelial cells are associated with airway mucus hypersecretion, inflammation and infection that begin early in life and lead, at an advanced stage of the disease, to severe airway obstruction with hyperviscous and adhesive airway mucus. Whether the abnormalities of airway mucus are already present at birth before infection is debatable. In CF, the impaired Cl and HCO3 secretion associated with increased epithelial Na+ absorption results in dehydration of airway mucus, decreased antimicrobial functions and impaired mucociliary clearance. Alterations in antibacterial peptide function, as well as the increased mucin expression and secretion (MUC 5AC and MUC 5B), are important biochemical factors responsible for the propensity for infection in CF airways. Alterations in mucin and lipid composition induce an increased viscosity and adhesiveness to the airways that can affect the mucociliary and cough transport. The increased content of pro-inflammation cytokines such as interleukin-8 (IL-8) suggest that, before infection, airway inflammation occurs very early in CF. The development of non-invasive techniques and humanised animal models (xenografts) represents a major opportunity to identify early abnormalities in CF airway mucus.

Section snippets

INTRODUCTION

Defective expression and function of the cystic fibrosis transmembrane conductance regulator (CFTR) in cystic fibrosis (CF) airway epithelial cells are associated with mucus hypersecretion, inflammation and infection that begin early in life and lead to a persistent vicious cycle with marked airway obstruction and infection responsible for the morbidity and mortality in patients with CF.

Although thick and adhesive airway mucus represents a hallmark of the disease in CF patients at an advanced

Ion and water composition of CF airway mucus: effect on mucociliary transport

The mucus covering the airway mucociliary epithelium is generally described as a biphasic layer composed of a periciliary sol layer in which the cilia beat and a more superficial gel layer which constitutes an efficient barrier against micro-organisms.

The hydration of the periciliary fluid layer under homeostatic conditions is mainly regulated by luminal/basolateral water transport coupled to active transepithelial Na+ transport. The accompanying absorptive movement of Cl and water occurs

RHEOLOGICAL PROPERTIES OF CF AIRWAY MUCUS AND RELATED ABNORMAL MUCOCILIARY AND COUGH TRANSPORT PROPERTIES

The airway mucus is a very complex biological fluid that is characterised by flow (viscosity) and deformation (viscoelastic) properties as well as surface properties that are independent of the viscoelastic properties and control the capacity of airway mucus to protect and lubricate the airway mucosa. In CF, there are no data demonstrating that the native airway mucus is hyperviscous. In human bronchial airway xenograft, the viscosity of airway fluid inside the lumen of the human CF tracheal

IN VIVO MODELS FOR STUDYING CF AIRWAY MUCUS

Most of the studies of CF airway mucus have been carried out on expectorated sputum at a stage of the disease where hypersecretion is already present. It is much more difficult to collect the airway mucus at an early stage of the disease and to compare the results with that obtained in healthy control subjects, due to the small volume of secreted mucus. To collect “normal” airway mucus and determine the ASL composition in intact normal and CF airways, very small samples were collected using

RESEARCH DIRECTIONS

  • Develop non-invasive and in vivo techniques to identify early airway mucus disorders in CF.

  • Identify the nature of antibacterial factors impaired in CF airway mucus.

  • Define the role of bacteria (Staphylococcus aureus and Haemophilus influenzae) and viruses identified early in CF, in airway mucus disorders.

  • Better define the relationship between CFTR dysfunction and CF airway mucus disorders.

  • Develop strategies focusing on CF airway mucus disorders.

PRACTICE POINTS

  • There are no data to support the hypothesis that uninfected mucus in the newborn with cystic fibrosis has abnormal viscosity or elasticity.

  • Cystic fibrosis airways have an increased propensity to inflammation that may occur in the absence of overt infection. Furthermore the risk of infection is increased by the inactivation of one or more antimicrobial peptides as well as the development of abnormal mucus properties.

  • In purulent secretions (sputum), the DNA/F-actin polymer network and alterations

Acknowledgements

We would like to thank the “Association Vaincre la Mucoviscidose” for support in the research work that has been conducted in our laboratory.

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