PHYSICAL AND FUNCTIONAL-PROPERTIES OF AIRWAY SECRETIONS IN CYSTIC-FIBROSIS - THERAPEUTIC APPROACHES

The airway secretions which line the respiratory tract form a biphasic layer composed of an aqueous 'sol' layer and a more superficial 'gel' layer. In the sol layer, also described as the 'periciliary' layer or 'airway surface fluid', the cilia beat and relax. The lubricant sol l ayer enables the gel mucus present at the tips of the cilia to be tran sported by the ciliary beating of the ciliated cells. Due to difficult ies with sampling, little is known about the physical and biochemical properties of the sol layer. The gel layer is composed of high molecul ar weight glycoproteins (mucins) linked with proteins and lipids. They form a gel network with a high water content (95%) and theologic and physical properties (viscoelasticity, adhesivity) adapted in normal co nditions to protect the airway mucosa, particularly through mucociliar y transport. The adhesive properties of mucus, which are influenced by its lipid composition and degree of hydration, are very important in controlling the efficacy of mucus transport through ciliary activity a nd coughing. An intermediate viscosity and elasticity is required for optimal mucociliary transport. In obstructive airway diseases, either of genetic origin, such as cystic fibrosis (CF), or acquired (acute or chronic bronchitis), and particularly during inflammatory and infecti ous episodes, mucus dehydration is associated with an increase in secr eted or transudated molecules and with marked augmentation of DNA cont ent. These abnormalities contribute to the increased viscosity and adh esivity of the airway secretions and are responsible for their abnorma lly low transport rate by ciliary activity and for inefficient cough c learance. In view of these alterations in the physical and functional properties of CF airway secretions, pharmacologic approaches should ai m to rehydrate the mucus and to restore normal mucociliary or cough tr ansport by stimulating chloride ion secretion (i.e. using UTP or ATP a ssociated with amiloride in order to block sodium ion and water reabso rption). During acute episodes of infection, recombinant human DNase ( rhDNase) may rapidly prevent mucus stasis by improving its theologic p roperties. Lubrication of the mucus at the sol phase interface by 'sur factant' therapy may also represent a very promising therapeutic persp ective to reduce the hyperviscosity and hyperadhesivity of airway secr etions.