We hypothesize that allergic asthmatics are less capable in resolving inflammatory cells after viral airway infection as a consequences of impaired expression of indoleamine 2,3-dioxygenase.
ID
Bron
Verkorte titel
Aandoening
Virus-induced exacerbations in allergic asthmatics.
keywords: rhinovirus, exacerbation, allergy, asthma
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
1. Common cold questionnaire;<br>
2. Asthma symptom score;<br>
3. FEV1;<br>
4. PC20 methacholine;<br>
5. Inflammatory cell numbers;<br>
6. Indoleamine 2,3-dioxygenase expression;<br>
7. Apoptotic markers.
Achtergrond van het onderzoek
To investigate whether allergic asthmatics have an impaired capability to resolve inflammatory cells after viral airway infection, we will expose healthy individuals and allergic asthmatics to rhinovirus type 16. Volunteers will undergo two bronchoscopies to collect material before and after infection. In addition, lung function testing and asthma and common cold questionnaires will be included.
Doel van het onderzoek
We hypothesize that allergic asthmatics are less capable in resolving inflammatory cells after viral airway infection as a consequences of impaired expression of indoleamine 2,3-dioxygenase.
Onderzoeksopzet
1. 2 days prior to infection;
2. 4 days after infection (lung function testing only);
3. 6 days after infection.
Onderzoeksproduct en/of interventie
Healthy volunteers and allergic asthma patients will be infected by rhinovirus-type 16 (10 TCID50) by spraying the virus into the nasal cavity, leading to mild common cold symptoms. In general, these symptoms will be more pronounced for allergic astmatics and will be scored daily by the volunteers (through a modified asthma control questionnaire (ACQ) and a common cold questionnaire (CCQ)). We expect that the increased symptoms scores in asthmatics is associated with enhanced inflammation of the airways. We will therefore include several inflammatory markers in our study. We used cytokine levels in bronchoalveolar lavage fluid to calculate the power of the study. In this study we are trying to correlate symptoms, inflammation, viral load and relevant biomarkers of IDO-mediated tryptophan degradation in blood and lavage fluid. We will also include non-invasive techniques to measure these end-points through NO measurements and exhaled breath condensate.
Algemeen / deelnemers
Academic Medical Center
University of Amsterdam
P.O. Box 22700
Peter J. Sterk
Amsterdam 1100 DD
The Netherlands
+31 (0)20 5668137 or +31 (0)20 5664356
p.j.sterk@amc.nl
Wetenschappers
Academic Medical Center
University of Amsterdam
P.O. Box 22700
Peter J. Sterk
Amsterdam 1100 DD
The Netherlands
+31 (0)20 5668137 or +31 (0)20 5664356
p.j.sterk@amc.nl
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
Allergic asthmatics:
1. Age between 18 and 40 yrs;
2. PC20 to methacholine below 8 mg/ml;
3. Skin-prick test positive to a least one common allergen.
Healthy:
1. Age between 18 and 40 yrs;
2. PC20 to methacholine above 16 mg/ml;
3. Skin-prick test negative to all common allergens.
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
Allergic asthmatics:
1. Current smokers;
2. Ex-smokers with more than 5 packyears;
3. Pre-FEV1 below 80% predicted;
4. Oral or inhaled steroid use;
5. Exacerbations during the past 6 weeks;
6. Underlying pulmonary condition other than asthma;
7. Non-pulmonary underlying conditions that may interfere with the study or that may result in unacceptable risk for the patient (incl. pregnancy);
8. Concomittant drug use (except short-acting bronchodilators);
9. Daily contact with young children (<2yrs).
Healthy:
1. Current smokers;
2. Ex-smokers with more than 5 packyears;
3. Pre-FEV1 below 80% predicted;
4. Oral or inhaled steroid use;
5. Underlying pulmonary condition other than asthma;
6. Non-pulmonary underlying conditions that may interfere with the study or that may result in unacceptable risk for the patient (incl. pregnancy);
7. Concomittant drug use (except short-acting bronchodilators);
8. Daily contact with young children (<2yrs).
Opzet
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