Asthma
Conditions
Keywords
Asthma, Allergen challenge, Airway responsiveness, Prostaglandins, Eicosanoids
Brief summary
The study is part of a research programme into mechanisms of asthmatic airway obstruction, focusing on the role of lipid mediators such as the prostaglandins. To this end the effect of a non-steroidal anti-inflammatory drug, the selective COX-2 inhibitor etoricoxib, will be evaluated in the allergen challenge setting in twelve subjects with intermittent allergic asthma. Active treatment for 10 to 13 days will be compared with an identical study period with no treatment in a cross-over, randomised design. Rising dose allergen challenges will be performed on three occasions to assess possible changes in airways responsiveness. Sampling of blood, urine, saliva and sputum will be done to allow for analyses of the production of prostaglandins and other lipid mediators, of the efficacy of COX-2 inhibition as well as of regulation of immune cells. It is hypothesized that inhibition of COX-2 by virtue of inhibition of bronchoprotective prostaglandin E2 leads to a slightly exaggerated airway response to allergen exposure.
Interventions
DRUGEtoricoxib
90 mg/day orally for 10-13 days
Sponsors
Karolinska Institutet
Barbro Dahlen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Female or male aged 18 to 55 years inclusive * A history of asthma for at least 6 months with at least one of the following: * response to standard asthma treatment * episodic wheezing * change in lung function over short periods of time * A positive methacholine challenge test as evidenced by a PD20 ≤7256 µg cumulated dose within 8 weeks prior to screening or at the screening visit. * Stable intermittent asthma, only using bronchodilator therapy as needed for the last 4 weeks. * FEV1 ≥ 75% of predicted. * A positive skin prick test to pollen (grass, birch, mugwort) or animal dander (dog, cat)
Exclusion criteria
* Known or suspected hypersensitivity to coxibs * Any significant respiratory disease other than asthma * Respiratory tract infection within 4 weeks before inclusion. * Any significant disease or disorder which, in the opinion of the investigator, may put the patient at risk because of participation in the study. In particular previous or present history of cardiovascular disease, ie myocardial infarction, stroke, severe hypertension, left ventricular heart failure and/or pulmonary hypertension are strict
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Allergen PD20 FEV1 | 10 to 13 days |
Secondary
| Measure | Time frame |
|---|---|
| Urinary prostaglandin E2 and D2 concentrations | 10-13 days |
Countries
Sweden
Outcome results
None listed