Duration of effect of single-dose inhaled fluticasone propionate on AMP-induced bronchoconstriction

Abstract

Airway hyperresponsiveness induced by adenosine-59-monophosphate (AMP) is regarded as a reliable model for allergic asthma and for the evaluation of anti-asthmatic drugs. Single-dose inhaled corticosteroids (ICS) are known to be protective in this model, but the duration of action of these drugs in this model has never been studied.The duration of ICS protection was determined by administration of single-dose fluticasone propionate (FP; 1,000 mg) up to 26 h before AMP challenge. A randomised, double-blind, placebo-controlled, four-way crossover study was performed in 13 mild asthmatics (mean¡SD predicted forced expiratory volume in one second (FEV1) 98¡7%). Each subject received placebo and FP (at 26, 14 or 2 h prior to the AMP challenge). Furthermore, the marker exhaled nitric oxide (eNO) was studied after administration at these time points to investigate whether eNO also demonstrates the duration of action of ICS.The doubling concentrations difference (DCD) of AMP causing a 20% fall in FEV1, when FP was administered 26, 14 or 2 h prior to challenge, was significantly increased as compared with placebo: DCD (95% confidence interval) at 26 h, 0.73 (0.20-1.26), p=0.008; 14 h, 1.50 (0.99-2.01), pv0.001; and 2 h, 2.89 (2.37-3.40), pv0.001. However, eNO was not significantly affected at these time points.In conclusion, a single dose of 1,000 mg inhaled fluticasone propionate protects against adenosine-59-monophosphate airway hyperresponsiveness up to 26 h after dosing. This study suggests that adenosine-59-monophosphate challenge can be used as a sensitive marker to study the duration of action of inhaled corticosteroids.

Rapid Selective Priming of FcαR on Eosinophils by Corticosteroids

“…In these experiments, this corticosteroid could inhibit asthma symptoms within 10 min (35). We obtained data showing similar rapid effects in human asthmatics treated with fluticasone (36). These data underscore the importance of nongenomic mechanisms involved in the effects of corticosteroids during treatment of allergic asthma.…”

The role of endogenous and exogenous AMP in asthma and chronic obstructive pulmonary disease

“…Finally, it has been shown that the PC 20 AMP, in contrast to the PC 20 methacholine or the concentration of exhaled nitric oxide, significantly improves within 2 hours of a single inhaled dose as low as 100 mg of fluticasone propionate. 60,85 The mechanism underlying this phenomenon is not well established; it has been proposed that it involves an effect on airway mucosal blood flow and microvascular permeability. Although the rapid protective effect by a single dose of an inhaled corticosteroid has never been studied in patients with asthma taking chronic inhaled corticosteroids, the extreme sensitivity of AMP to these drugs could be a relative disadvantage to its potential clinical applications.…”

Long-Term Safety and Efficacy of Fluticasone/Formoterol Combination Therapy in Asthma

“…30,31 The ICS, fluticasone propionate (fluticasone), delivers a potent and sustained anti-inflammatory effect. 17,[32][33][34] The LABA, formoterol fumarate (formoterol), has a fast onset of action and a prolonged bronchodilatory effect. 5,[35][36][37][38] Fluticasone and formoterol have now been combined in a single aerosol inhaler (fluticasone/formoterol; flutiform Ò ).…”

“…60,61 The safety and efficacy of both fluticasone and formoterol are extensively documented in the literature. 5,17,[32][33][34][35][36][37][38] The administration of fluticasone/formoterol from a single pMDI allows patients to experience rapid bronchodilation after dosing while providing sustained anti-inflammatory effects, via a commonly used and familiar device. 26 Together, these factors may provide incentives for patients to adhere to their treatment regimen and achieve better asthma control.…”