Elemental Composition of Human Airway Surface Fluid in Healthy and Diseased Airways

Abstract

The fluid that covers the surface of conducting airways (airway surface fluid, ASF) is a critical component of one of the first defense mechanisms of the lung against microbial and other environmental insults. Despite its physiologic importance, ASF is one of the only fluids in the human body whose composition remains poorly defined and understood. Attempts to analyze ASF have been hampered greatly by the fact that it exists only as a very thin layer covering the mucosal surface of airway epithelia. To overcome some of these limitations, we have applied ultramicroanalytic techniques to microsamples collected in human airways in vivo. In contrast to previous thinking from studies on sputum samples, ASF collected from healthy airways contains much less Na and Cl (approximately 45% less) and much more K (around 600% more) than extracellular fluid or plasma (ECF), which shows that steep ion gradients exist across normal airway epithelia. These differences also show that ASF composition must be regulated and maintained by active electrolyte transport processes of airway epithelia and that it is not merely the evaporated residue of isotonic secretions or extracellular fluid exudate. However, in patients with sustained airway irritation, infection, or cystic fibrosis, we find that ASF composition appears to become more isotonic with respect to plasma and much more hypotonic in patients with asthma.

Sodium chloride increases the ciliary transportability of cystic fibrosis and bronchiectasis sputum on the mucus-depleted bovine trachea.

“…The only analyses thus far reported used methods likely to have perturbed its composition significantly. One estimate, using the application of filter paper to the tracheae of three CF individuals yielded salinity values higher than were found in normal individuals (16). However, the potassium concentration was high compared with that in laryngectomy mucus, raising the possibility of cell damage.…”

New concepts of the pathogenesis of cystic fibrosis lung disease

“…In the early to mid-1990s, a novel hypothesis for airways9 defence emerged that focused on the role of antimicrobial peptides in ASL to provide a chemical shield on the airway surface as the primary innate defence [35][36][37]. For this shield to be effective, two processes must be normally regulated by the airway epithelium.…”

Calcium‐dependent binding of uteroglobin (PCB‐BP/CCSP) to negatively charged phospholipid liposomes

“…In contrast, PCB-BP/uteroglobin needs calcium concentrations in the mM range. Calcium concentrations in the lining fluid of conducting airways has been reported to be around 4 mM in humans [26].…”