Airway surface liquid (ASL)

Airway surface liquid (ASL) is a thin (∼5–100 μm) bi-phasic layer at the apical side of the airway epithelium, composed of a periciliary liquid layer enabling ciliary movement and an outer mucus gel layer that traps and removes inhaled particles and pathogens via mucociliary clearance[1][3][4][5][6]. ASL composition and volume are regulated by electrolyte transport, notably chloride secretion via CFTR channels and sodium absorption via ENaC; disruption of these ion channels, such as in cystic fibrosis, results in ASL dehydration, impaired clearance, and increased vulnerability to infection and chronic inflammation[3][5][7]. ASL is not a molecular drug target, but its hydration and composition are critical endpoints in airway disease treatment. Drugs that modulate ion channels (CFTR, ENaC) or use osmotic agents can impact ASL properties and are used in managing cystic fibrosis and related pulmonary conditions[3][7]. Airway surface liquid should be recognized as an important physiological compartment and not as a canonical drug target. When looking for therapeutically actionable targets, focus instead on the molecular components that regulate ASL—such as CFTR (cystic fibrosis transmembrane conductance regulator) or ENaC (epithelial sodium channel).

Other names

Airway surface fluidAirway lining fluidRespiratory surface liquidEpithelial lining fluid

ENaC inhibitors reduce Na+ absorption, increasing ASL volume and improving mucociliary clearance. CFTR modulators restore Cl− and HCO₃⁻ secretion, improving ASL hydration and pH, and enhancing host defense. Osmotic agents (e.g., hypertonic saline) draw water onto the airway surface, increasing ASL volume.