Effects of once daily dosing with inhaled budesonide on airway hyperresponsiveness and airway inflammation following repeated low‐dose allergen challenge in atopic asthmatics

Gauvreau,; Sulakvelidze,; Watson, J. R.; Inman,; Rerecich,; O'Byrne,

doi:10.1046/j.1365-2222.2000.00860.x

Cited by 31 publications

(27 citation statements)

References 33 publications

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“…Accordingly, the baselines were very similar for all outcome variables and statistical calculations yielded the same final results irrespective of adjustments for baseline differences. With a three-period design and 4 days of allergen-PD5 exposure, GAUVREAU et al [18] demonstrated sufficient washout with 1 week.…”

Section: Discussionmentioning

confidence: 99%

“…In this challenge setting, patients with allergic asthma inhale fixed doses of allergen that are titrated to cause minimal bronchoconstriction and administered once daily on between four and 10 consecutive weekdays [17,18]. The procedure generates increased airway hyperresponsiveness to direct bronchoconstrictors and elevations in exhaled nitric oxide fraction (FeNO) and in inflammatory markers in sputum [17,18].…”

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confidence: 99%

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Effect of formoterol with or without budesonide in repeated low-dose allergen challenge

Dahlén¹,

As²,

Ihre³

et al. 2009

European Respiratory Journal

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The use of combination therapy in mild asthma is debated. The current authors evaluated the effects of formoterol alone and a formoterol/budesonide combination inhaler on asthma deterioration induced by repeated low-dose allergen exposure.In total, 15 subjects with intermittent allergic asthma inhaled low doses of allergen on seven consecutive weekdays in a three-period, crossover, double-blind, double-dummy comparison between formoterol 4.5 mg Turbuhaler TM , budesonide 160 mg/formoterol 4.5 mg Turbuhaler TM and placebo, each taken as two puffs 30 min after allergen dosing. The outcome variables were: provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (PD20), exhaled nitric oxide fraction (FeNO), sputum eosinophils and prostaglandin D 2 , and diary card recordings of symptoms (on a scale of 0-10), short-acting b 2 -agonist use and evening forced expiratory volume in one second (FEV1). With placebo treatment, allergen exposure caused significant increases in airway hyperresponsiveness (geometric mean (coefficient of variation) PD20: 397 (98) mg before versus 168 (82) mg after), FeNO (mean¡SD 46¡31 ppb before versus 73¡46 ppb after) and asthma symptom score (mean¡SD 0.39¡0.55 before versus 0.68¡0.67 after). Budesonide/formoterol abolished these changes and significantly improved baseline FEV1. Formoterol alone, while providing symptom relief, was no better than placebo in protecting against the allergen-induced increase in airway inflammation.Signs of deteriorating asthma, provoked by low-dose allergen, are prevented by short-term use of budesonide/formoterol but not by temporary use of formoterol alone.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Effect of formoterol with or without budesonide in repeated low-dose allergen challenge

Dahlén¹,

As²,

Ihre³

et al. 2009

European Respiratory Journal

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“…However, investigations of mechanisms of airway inflammation in this particular model have been rather limited so far, and findings in peripheral blood are largely negative [5,7,9]. In a diluent controlled evaluation of the challenge, the percentage of eosinophils, interleukin-5 and eosinophil cationic protein in induced sputum were shown to increase [2], and early effects on eosinophils and macrophages in bronchoalveolar lavage fluid have also been reported [9,10].…”

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confidence: 90%

“…The challenge model is, therefore, particularly suitable to investigate early events in the development of AHR, a central feature of the asthmatic phenotype. The relevance of the model is supported by the established effects of inhaled corticosteroids on AHR and sputum eosinophilia induced by the low-dose challenge procedure [7,8].…”

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confidence: 99%

“…For example, the allergen-induced early and late asthmatic response in the conventional highdose allergen challenge is associated with an increase in urinary levels of 9a11b-PGF 2 [12]. While the activation of eosinophils has been shown to occur in the low-dose challenge [2,7,8], the activation of mast cells has been less explored. It is becoming increasingly evident that the pathogenetic role of the eosinophil in asthmatic airway inflammation is uncertain [13].…”

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Early rise in exhaled nitric oxide and mast cell activation in repeated low-dose allergen challenge

Ihre

Gyllfors²,

Gustafsson³

et al. 2006

European Respiratory Journal

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Repeated low-dose allergen inhalation challenge mimics natural allergen exposure, providing a model for early mechanisms in the triggering of asthma. The current authors performed a controlled study to evaluate the time course of changes in exhaled nitric oxide fraction (Fe,NO) and urinary biomarkers of airway inflammation.Eight subjects with mild allergic asthma completed two 7-day repeated low-dose challenge periods, with diluent and allergen, respectively. Subjects were symptom free at inclusion and were investigated when not exposed to specific allergen. Pulmonary function and symptoms were followed, and Fe,NO and urinary mediators were correlated to changes in airway responsiveness to histamine and adenosine.Despite no change in pulmonary function (forced expiratory volume in one second mean¡SEM fall 0.3¡0.7 versus 0.6¡1.0%, for diluent and allergen, respectively) and no asthma symptoms, repeated allergen exposure, in contrast to diluent, caused significant increases in histamine responsiveness (2.3 doubling doses), an early and gradual increase in Fe,NO (up to a doubling from baseline) and a small increase in the mast cell marker 9a11b-prostaglandin F 2 after adenosine challenge.In conclusion, serial measurements of exhaled nitric oxide fraction have the potential to provide a very sensitive strategy for early detection of emerging airway inflammation and subsequent changes in airway hyperresponsiveness to histamine.

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Budesonide at different doses for chronic asthma

Adams

Bestall

Jones

2000

Cochrane Database of Systematic Reviews

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Effects of once daily dosing with inhaled budesonide on airway hyperresponsiveness and airway inflammation following repeated low‐dose allergen challenge in atopic asthmatics

Abstract: Both budesonide 100 microg and 400 microg inhaled once daily significantly reduces allergen-induced sputum eosinophilia after repeated low dose challenge; however, only the higher dose also attenuates the allergen-induced airway hyperresponsiveness.

Cited by 31 publications

References 33 publications

Effect of formoterol with or without budesonide in repeated low-dose allergen challenge

Effect of formoterol with or without budesonide in repeated low-dose allergen challenge

Early rise in exhaled nitric oxide and mast cell activation in repeated low-dose allergen challenge

Budesonide at different doses for chronic asthma

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