Bronchial responsiveness to leukotriene D4 is resistant to inhaled fluticasone propionate - 17/08/11
Reprint requests: Barbro Dahlén MD, PhD, Division of Respiratory Medicine and Allergy, Department of Medicine, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden.Stockholm, Sweden
Abstract |
Background |
Inhaled corticosteroids are highly effective in asthma, reducing inflammatory markers and bronchial hyperresponsiveness. Cysteinyl-leukotrienes are major mediators of airway obstruction and display proinflammatory effects. Although the synthesis of leukotrienes is not affected by corticosteroid treatment, the influence of corticosteroids on the leukotriene pathway remains unresolved.
Objective |
We investigated whether or not bronchial responsiveness to leukotriene (LT) D4 is reduced by fluticasone propionate in subjects with asthma.
Methods |
In 13 subjects with mild asthma, inhalation challenges with methacholine and LTD4 were performed on consecutive days before and after 2 weeks of treatment with inhaled fluticasone 500 μg, twice daily, in a double-blind, randomized, placebo-controlled study with crossover design and 3 weeks of washout between periods. Exhaled nitric oxide was measured as a marker of corticosteroid responsiveness, and baseline urinary LTE4 concentrations as an index of cysteinyl-leukotriene biosynthesis.
Results |
Fluticasone produced a significant decrease in methacholine responsiveness, corresponding to 2.6-fold shift in the PD20 FEV1, and a significant reduction in the levels of exhaled nitric oxide. By contrast, bronchial responsiveness to LTD4 in the same subjects was unaffected by fluticasone, as were urinary LTE4 concentrations.
Conclusion |
These new data indicate that neither the biosynthesis nor the actions of leukotrienes appear to be sensitive to inhaled corticosteroids.
Clinical implications |
The study provides mechanistic support for the additive therapeutic efficacy of antileukotrienes and inhaled corticosteroids in asthma.
El texto completo de este artículo está disponible en PDF.Key words : Asthma, bronchoprovocation, urinary leukotriene E4, leukotriene D4 responsiveness, methacholine responsiveness, exhaled nitric oxide, inhaled corticosteroids
Abbreviations used : EAR, FENO, ICS, LAR, LT
Esquema
| Supported by Karolinska Institutet, the Centre for Allergy Research and the Stockholm County Council, and the following Swedish foundations: Heart Lung Foundation, Association Against Asthma and Allergy, Consul Bergh’s Foundation, Medical Research Council (projects 14X-9071 and 74X-15067), and the Foundation for Health Care Sciences and Allergy Research (Vårdal). Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest. |
Vol 118 - N° 1
P. 78-83 - juillet 2006 Regresar al número
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