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Improving Asthma Rescue Treatment: Using Inhaled Corticosteroids to Enhance β2-adrenergic Bronchodilation

Wanner A.

RDD Europe 2017. Volume 1, 2017: 19-24.

Abstract:

β2-adrenergic agonists including albuterol are organic cations and owing to their hydrophilicity, their entry into non-neuronal cells in the airway requires active transport. The glucocorticoid-sensitive organic cation transporter 3 (OCT3) is expressed on human airway and airway vascular smooth muscle, and our studies have shown that the glucocorticoid action on organic cation uptake occurs within minutes, does not involve gene transcription or protein synthesis, is not mediated through classical steroid receptors, and is cell membrane-linked. This non-genomic glucocorticoid action could increase the concentration of β2-adrenergic agonists at β2-adreno-receptor sites and potentiate β2-adrenergic smooth muscle relaxation. To test this hypothesis in vivo, the acute bronchodilator effect of inhaled albuterol (180 μg) co-administered with inhaled mometasone (400 μg) or placebo was determined in patients with moderate asthma. The albuterol-induced increase in FEV1 was 19% with mometasone and 10% with placebo (p<0.05). This observation could provide the basis for the development of new rescue formulations by combining an inhaled short-acting β2-adrenergic agonist with a glucocorticoid.