Epithelial Na+/K+ Imbalance and Impaired Na+/K+-ATPase Activity as Surface Markers of Airway Remodelling in Obstructive Sleep Apnea.

Airway remodelling in obstructive sleep apnea encompasses diverse histopathological and neuromuscular alterations, yet surface-level epithelial changes and ionic characteristics remain insufficiently studied. Using time-of-flight secondary ion mass spectrometry, this study identified disrupted epithelial ionic homeostasis in the upper airway. Inferior turbinate specimens were collected from 18 patients with obstructive sleep apnea and 22 controls undergoing upper airway surgery. Compared with controls, specimens from patients with obstructive sleep apnea demonstrated significantly elevated sodium-to-potassium ratios (1.66 ± 1.38 vs. 0.83 ± 0.38, p = 0.033), with a marginal association persisting after adjustment for age and body mass index (p = 0.057). Immunohistochemistry revealed reduced sodium-potassium adenosine triphosphatase expression in the epithelium of obstructive sleep apnea specimens (p = 0.0077), while histology showed epithelial metaplasia and inflammatory changes. Among several machine learning classifiers, the random forest model achieved the highest diagnostic performance, yielding an area under the curve of 0.7928 and consistently identifying the sodium-to-potassium ratio as the most discriminative feature. Together, these findings demonstrate that disrupted sodium-to-potassium balance and diminished sodium-potassium adenosine triphosphatase expression constitute epithelial signatures in obstructive sleep apnea. Such ionic dysregulation may impair membrane potential and pharyngeal muscle responsiveness, thereby promoting airway collapsibility. Given the established role of ion channels in neuromuscular regulation, the epithelial sodium-to-potassium ratio may represent not only a diagnostic biomarker but also a potential predictor of therapeutic response to potassium channel-targeted interventions.