Asthma
Conditions
Interventions
16 patients will inhale 100 *g of salmeterol 30 minutes before bronchial
instillation of house dust mite allergen (selected on low LPS content, n=8) or
house dust mite allergen with additional LPS (
Sponsors
Academisch Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: * Intermittent to mild asthmatics between 18 and 45 years of age * Allergy for house dust mite documented by a positive RAST * No clinically significant findings during physical examination and hematological and biochemical screening * At spirometry FEV1 more than 70% of predicted value * Stable asthma while treated with fluticasone propionate 100*g bid during 2 weeks before the study.
Exclusion criteria
Exclusion criteria: * Comorbidity * A history of smoking within the last 12 months, or regular consumption of greater than three units of alcohol per day * Exacerbation and/or the use of oral steroids within the 4 weeks before start of run in. * Administration of any investigational drug within 30 days of study initiation * Donation of blood within 60 days, or loss of greater than 400 ml of blood within 12 weeks of study initiation * History of enhanced bleeding tendency * History of serious drug-related reactions, including hypersensitivity * Inability to use only the run-in medication plus salbutamol rescue medication supplied for this study. If subjects use other pulmonary medications these will be replaced by the run-in medication.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Neutrophil, eosinophil and mast cell responses * Total leukocyte counts and differentials (BAL and blood) * Neutrophil activation (surface expression of CD11b as assessed by FACS) * Neutrophil degranulation (myeloperoxidase (MPO); by ELISA) * Eosinophil degranulation (eosinophil cationic protein (ECP); by ELISA) * Mast cell degranulation (chymase, tryptase, IP-10, c-kit ligand) Activation of cytokine network * Proinflammatory cytokines: TNF-*, IL-6, IL-5 (BAL and serum) * Anti-inflammatory cytokines : IL-10 Activation of the chemokine network * CXC chemokines: IL-8, GRO-* * CC chemokines: MCP-1, MIP-1*, MIP-1* | — |
Secondary
| Measure | Time frame |
|---|---|
| * Alveolar macrophages will be isolated using CD71 microbeads and autoMACS. RNA will be isolated from these cells and used for micro-array and multiplex ligation-dependent probe amplification (MLPA) (12). MLPA analyses will focus on activation of inflammation genes including TF (12,13,14). * Lung functions will be assessed before and after the provocations | — |
Countries
Netherlands
Outcome results
None listed