The effect of inhaled corticosteroids on airway Na/K ATPase content in patients with asthma

Abstract

Background: The Na+/K+ ATPase may play a role in bronchoconstriction in asthma: Through active building of ion gradients across cell membranes, the Na+/K+ ATPase contributes to regulation of intracellular Ca2+ in airway smooth muscle via the Na+/Ca2+ exchanger. Corticosteroids increase Na+/K+ ATPase content in striated muscle but the effect has not been investigated in human airways. Aims and Objectives: To investigate the effect of inhaled corticosteroids (ICS) on the airway Na+/K+ ATPase content in patients with type 2 high (T2-high) and T2-low asthma. Methods: The RECONSTRUCT-study was a prospective intervention study with 50 steroid-free patients with asthma and 10 healthy controls. Airway Na+/K+ ATPase content was determined by the vanadate-facilitated [H3]-ouabain method in mucosal cryobiopsies before and after 6 weeks of daily treatment with 1600 µg budesonide. Patients were stratified into T2-high (FeNO≥25 ppb) and T2-low asthma (FeNO Results: Airway Na+/K+ ATPase content was comparable in healthy controls: Mean: 148ρmol/g (95% CI: 120-177), patients with T2-high asthma: 177ρmol/g (95% CI: 157-198) and patients with T2-low asthma: 189ρmol/g (95% CI: 156-222), P=0.20. After treatment with ICS, Na+/K+ ATPase content increased by 14% in patients with T2-high asthma to: 205ρmol/g (95% CI: 178-228), P=0.017, but not in patients with T2-low asthma: 201ρmol/g (95% CI: 174-228), P=0.54. Conclusion: Treatment with ICS increases airway Na+/K+ ATPase content in patients with T2-high asthma but not in patients with T2-low asthma. This effect could be protective against bronchoconstriction, but needs to be verified in further studies.