Modulation of the Ionic Milieu of the Airway in Health and Disease

Abstract

Airway surface liquid (ASL) is an integral part of lung defense mechanisms. Ion transport by airway epithelia regulates the volume and composition of this fluid. A better understanding of the mechanisms of ion transport will enable the development of new therapies for airway diseases associated with defects in these mechanisms. A useful model of a disease with abnormal airway epithelial ion transport is cystic fibrosis (CF), a distinct genetic syndrome of altered lung defense mechanisms characterized by chronic bacterial infection and a steady decline in lung function. Traditional therapies for CF include antibacterial drugs and augmentation of clearance of secretions, but investigators are now studying pharmacological approaches to target the more basic defect of the disease, i.e. abnormal sodium and chloride ion transport. Early treatment in childhood, prior to lung damage, might prevent or at least retard the decline in pulmonary function that remains the hallmark of CF. Ion transport dysfunction may also contribute to other airway diseases such as asthma and chronic bronchitis. Pharmacological intervention at this level may prove beneficial in these common lung diseases as well.

Role of Aquaporin Water Channels in Airway Fluid Transport, Humidification, and Surface Liquid Hydration

“…The water-transporting properties of the airways are thought to be important for humidification of inspired air and for maintaining the volume and composition of the airway surface liquid (ASL), the thin fluid layer covering airways. Abnormalities in ASL composition and volume have been proposed to play a major role in the pathophysiology of cystic fibrosis (Quinton 1994; Noone et al 1994; Boucher 1999; Pilewski and Frizzell 1999; Wine 1999) and other diseases of the airways such as asthma and bronchitis (Anderson et al 1982; Yager et al 1995; Freed and Davis 1999). Evaporative water loss in the airways is thought to drive water influx from capillaries and interstitium into the ASL by the creation of an osmotic gradient.…”