Rapid effect of inhaled fluticasone propionate on airway responsiveness to adenosine 5′-monophosphate in mild asthma

Ketchell, R.I.; Jensen, M W; Lumley, P. J.; Wright, A.; Allenby, Mark I.; O’Connor, Brian

doi:10.1067/mai.2002.128486

Cited by 93 publications

(81 citation statements)

References 10 publications

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“…Harvey et al demonstrated that in human bronchial epithelial cells, aldosterone decreases Ca 2+ levels via a non-genomic mechanism (Harvey et al 2001). Ketchell et al reported a rapid, topical anti-inflammatory action of inhaled fluticasone by a mechanism of action that remains unknown (Ketchell et al 2002). Here we propose a new opinion that nongenomic mechanism exists in rapid effects of GCs on allergic asthma reaction.…”

Section: Discussionmentioning

confidence: 76%

Rapid nongenomic effects of glucocorticoids on allergic asthma reaction in the guinea pig

Zhou¹,

Kang²,

Xie³

et al. 2003

Journal of Endocrinology

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Glucocorticoids (GCs) are routinely believed to work solely through genomic mechanisms. Recent evidence indicates that GCs can act at the membrane to exert rapid nongenomic effects on various tissues and cells. To ascertain whether nongenomic effects of GCs exist on the allergic asthma reaction, Hartley guinea pigs were sensitized with ovalbumin and challenged with the same antigen given by aerosol. Some animals received inhaled budesonide (3 mg/ml suspended in Hydroxypropyl methylcellulose vehicle) for 5 minutes before ovalbumin challenge; Other animals received saline or blank vehicle as control. We measured the changes of lung resistance and dynamic lung compliance, the pulmonary function used to evaluate allergic asthma severity. Inhaled budesonide inhibited allergic reaction within 10 minutes, which would preclude genomic-mediated responses that normally takes several hours to occur. This study infers for the first time that rapid nongenomic effect of GCs exists on allergic asthma reaction, and provides a new way to investigate nongenomic mechanism of GCs. Further study would raise the possibility of new therapeutic strategies for allergic disease including asthma.

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Section: Discussionmentioning

confidence: 76%

Rapid nongenomic effects of glucocorticoids on allergic asthma reaction in the guinea pig

Zhou¹,

Kang²,

Xie³

et al. 2003

Journal of Endocrinology

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“…Protection against the bronchoconstrictor effect of AMP appears to be a very sensitive response to corticosteroids in asthma [59,60] and is likely to be due to a rapid inhibitory effect of the inhaled corticosteroid on mucosal mast cells. A significant reduction in bronchoconstrictor response to inhaled AMP was seen as early as 2 h after a single inhalation of 100 mg fluticasone with no significantly greater protection seen with 1,000 mg fluticasone [61]. However, there was no protective effect against histamineinduced bronchoconstriction, suggesting that the inhaled corticosteroid was acting on mast cells.…”

Section: Rapid Anti-inflammatory Effects In Clinical Studiesmentioning

confidence: 79%

Scientific rationale for using a single inhaler for asthma control

Barnes¹

2007

European Respiratory Journal

138

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Clinical trials have recently demonstrated that using a budesonide/formoterol combination inhaler as regular maintenance treatment twice daily but also as a rescue therapy for breakthrough symptoms can provide more effective control of asthma, particularly in reducing exacerbations, than using a short-acting b 2 -agonist or formoterol as rescue therapy. This suggests that the corticosteroid component of the combination therapy plays an important role in rescue therapy.Formoterol as a rescue therapy is effective in relieving symptoms by relaxing airway smooth muscle but is also likely to have important inhibitory effects on mast cells, plasma exudation and neutrophilic inflammation.Inhaled corticosteroids have much more rapid suppressing effects on airway inflammation than previously recognised and the increased dose used as rescue therapy may prevent the increase in airway inflammation that occurs during the evolution of an exacerbation, thus preventing its development.It is likely that the molecular interactions between b 2 -agonists and corticosteroids also enhance the effect of the combination therapy as rescue therapy. There is now a strong scientific rationale for single inhaler therapy in asthma, but more research is now needed to better understand the mechanisms involved.

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“…A protective effect of fluticasone propionate (FP) against AMP challenge was observed within 2 h of administration and a protective effect of budesonide against hypertonic saline challenge was found within 6 h of administration [8,9]. Interestingly, the study with single-dose inhaled FP demonstrated protection towards AMP-AHR but not after direct challenge with histamine.…”

mentioning

confidence: 93%

“…A relatively high optimal dose of 1,000 mg FP, as indicated by the results of KETCHELL et al [8], was studied to determine the duration of protection after a single dose of FP.…”

mentioning

confidence: 99%

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

Luijk¹,

Kempsford²,

Wright³

et al. 2004

European Respiratory Journal

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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.

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Rapid effect of inhaled fluticasone propionate on airway responsiveness to adenosine 5′-monophosphate in mild asthma

Cited by 93 publications

References 10 publications

Rapid nongenomic effects of glucocorticoids on allergic asthma reaction in the guinea pig

Rapid nongenomic effects of glucocorticoids on allergic asthma reaction in the guinea pig

Scientific rationale for using a single inhaler for asthma control

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

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