Acute Effect of Mometasone on Beta-adrenergic Airway and Airway Vascular Relaxation in Severe Asthma
Status:
Completed
Trial end date:
2013-02-01
Target enrollment:
Participant gender:
Summary
Glucocorticosteroids inhibit the disposal of organic cations by blocking organic cation
transporters expressed by non-neuronal cells, thereby interfering with the inactivation of
the organic cations by intracellular enzymes. Beta2-adrenergic agonists are organic cations,
and the concentration of inhaled beta2-adrenergic agonists at beta2-adrenergic receptor sites
on smooth muscle is likely to be increased by inhaled glucocorticosteroids (ICS) by the ICS'
effect on the glucocorticosteroid-sensitive organic cation transporters. The investigators
have shown in human airway vascular smooth muscle cells that the glucocorticosteroid 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.
In the present proposal, the investigators wish to use different single doses of mometasone,
a clinically effective ICS, administered with or at different times before albuterol
inhalation in subjects with moderate persistent asthma who are obstructed at the time of
study.
With this approach the investigators will test the hypothesis that a single inhalation of
mometasone causes an acute, transient, dose-dependent potentiation of beta2-adrenergic
bronchodilation.
If the hypothesis that a single dose of mometasone acutely potentiates beta2-adrenergic
bronchodilation is correct, the results would have a significant impact on treatment
strategies involving ICSs and beta2-adrenergic agonists in patients with asthma.