Mild asthma, allergen induced inflammation
Conditions
Interventions
16 patients will inhale 100 ìg 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 (n=
Sponsors
Academic Medical Center Amsterdam, dept. Pulmonology
Eligibility
Inclusion criteria
Inclusion criteria: 1. Intermittent to mild asthmatics between 18 and 45 years of age; 2. Allergy for house dust mite documented by a positive RAST; 3. No clinically significant findings during physical examination and hematological and biochemical screening; 4. At spirometry FEV1 more than 70% of predicted value; 5. Able to communicate well with the investigator and to comply with the requirements of the study; 6. Stable asthma while treated with fluticasone propionate 100ìg bid during 2 weeks before the study; 7. Written informed consent; 8. No current smoking for at least 1 year and less than 10 pack years of smoking history; 9. Both male and female subjects are eligible for the study. Female subjects of child bearing potential will use adequate anti-conceptive precautions and will be tested for pregnancy at randomization.
Exclusion criteria
Exclusion criteria: 1. Comorbidity; 2. A history of smoking within the last 12 months, or regular consumption of greater than three units of alcohol per day; 3. Exacerbation and/or the use of oral steroids within the 4 weeks before start of run in; 4. Administration of any investigational drug within 30 days of study initiation; 5. Donation of blood within 60 days, or loss of greater than 400 ml of blood within 12 weeks of study initiation; 6. History of enhanced bleeding tendency; 7. History of serious drug-related reactions, including hypersensitivity; 8. Inability to use only the run-in medication plus rescue medication supplied for this study. If subjects use other pulmonary medications these will be replaced by the run-in medication.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Response of alveolar macrophages: 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). | — |
Primary
| Measure | Time frame |
|---|---|
| Neutrophil, eosinophil and mast cell responses: 1. Total leukocyte counts and differentials (BAL and blood); 2. Neutrophil activation (surface expression of CD11b as assessed by FACS); 3. Neutrophil degranulation (myeloperoxidase (MPO); by ELISA); 4. Eosinophil degranulation (eosinophil cationic protein (ECP); by ELISA); 5. Mast cell degranulation (chymase, tryptase, IP-10, c-kit ligand). Activation of cytokine network: 1. Proinflammatory cytokines: TNF-á, IL-6, IL-5 (BAL and serum); 2. Anti-inflammatory cytokines: IL-10. Activation of the chemokine network: 1. CXC chemokines: IL-8, GRO-á; 2. CC chemokines: MCP-1, MIP-1á, MIP-1â. | — |
Contacts
Public ContactJ.S. Zee, van der
P.O. Box 22700
Outcome results
None listed