In this study we will examine whether inhaled salmeterol inhibits house dust mite allergen-induced lung inflammation in mild asthmatics that are on maintenance treatment with low dose inhaled corticosteroids. If so, salmeterol may prove useful as…
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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 outcome
* 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
Background summary
Inhaled salmeterol was previously shown to inhibit lipopolysaccharide (LPS,
endotoxin) induced lung inflammation in healthy volunteers. Moreover, there are
indications that salmeterol inhibits allergen-induced bronchial inflammation in
asthma. Natural house dust and house dust mite extracts contain house dust mite
allergens as well as variable concentrations of LPS. Little is known about the
interaction of LPS-induced activation of the innate immune system and
allergen-induced allergic reactions
Study objective
In this study we will examine whether inhaled salmeterol inhibits house dust
mite allergen-induced lung inflammation in mild asthmatics that are on
maintenance treatment with low dose inhaled corticosteroids. If so, salmeterol
may prove useful as for maintenance treatment of asthma in addition to inhaled
corticosteroids. Moreover, we will examine the effect of LPS on house dust mite
allergen-induced bronchial inflammation in asthma.
Study design
This is an investigator-initiated, randomized, single centre, single blinded,
controlled study.
Intervention
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 (n=8). The control group will not
receive pre-treatment with salmeterol.
Study burden and risks
The burden associated with this study includes a screening visit, during which
an intake interview, a physical examination, routine blood tests and lung
function will be done. At the study day, all subjects will undergo two
bronchoscopies, which in our own experience as well as based on literature is
well tolerated by mild asthmatics. Each bronchoscopy will be preceded by a
blood draw (2 x 40 mL). The risk of and discomfort caused by bronchial
instillation of LPS is small and limited to a moderate rise in body
temperature. Allergen may induce bronchus obstruction in patients who did not
receive pre-treatment with salmeterol. This will be monitored by spirometry and
Atrovent 40 *g will be available as rescue medication during the study for all
subjects. The results of the study may be important for the group of asthmatic
patients as it will shed light on the interaction of LPS and allergen on the
bronchial inflammation in asthma. Salmeterol is primarily regarded as a
bronchodilatory drug, but it was shown to inhibit LPS induced bronchial
inflammation in healthy subjects. Moreover, there are some indications that it
also inhibits allergen-induced bronchial inflammation in asthmatics.
Demonstration of inhibition of allergen and allergen/LPS-induced bronchial
inflammation in asthmatics will broaden the applicability of salmeterol for
maintenance treatment for all groups of allergic asthma.
Meibergdreef 9
1105 AZ Amsterdam
NL
Meibergdreef 9
1105 AZ Amsterdam
NL
Listed location countries
Age
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-004045-28-NL |
| ClinicalTrials.gov | NCT1807 |
| CCMO | NL23834.018.08 |