The Effect of Inhaled Salmeterol on Inflammation after Bronchial Instillation of Allergen or Allergen/Lipopolysaccharide in Asthma.

Conditions: Asthma
10006436

Registration Number: NL-OMON33541

Lead Sponsor: Academisch Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 32

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

* 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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Neutrophil, eosinophil and mast cell responses<br /><br>* Total leukocyte counts and differentials (BAL and blood)<br /><br>* Neutrophil activation (surface expression of CD11b as assessed by FACS)<br /><br>* Neutrophil degranulation (myeloperoxidase (MPO); by ELISA)<br /><br>* Eosinophil degranulation (eosinophil cationic protein (ECP); by ELISA)<br /><br>* Mast cell degranulation (chymase, tryptase, IP-10, c-kit ligand)<br /><br>Activation of cytokine network<br /><br>* Proinflammatory cytokines: TNF-, IL-6, IL-5 (BAL and serum)<br /><br> Anti-inflammatory cytokines : IL-10<br /><br>Activation of the chemokine network<br /><br>* CXC chemokines: IL-8, GRO-<br /><br> CC chemokines: MCP-1, MIP-1, MIP-1</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>* Alveolar macrophages will be isolated using CD71 microbeads and autoMACS. RNA<br /><br>will be isolated from these cells and used for micro-array and multiplex<br /><br>ligation-dependent probe amplification (MLPA) (12). MLPA analyses will focus on<br /><br>activation of inflammation genes including TF (12,13,14).<br /><br><br /><br>* Lung functions will be assessed before and after the provocations</p><br>