asthma virus-induced asthma exacerbation
Conditions
Interventions
In part 2 all participants will undergo a RV16 infection.
Sponsors
Academisch Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Asthmatic patients part 1: Adult-onset eosinophilic asthma patients with a physician*s diagnosis of asthma that started after the age of 18. Stable on asthma medication, no exacerbation or changes in asthma medication in the past 4 weeks. Non-smoking, or ex-smoking (3%. Atopic and non-atopic patients will be distinguished based on total serum IgE. Atopy will be defined as a serum IgE levels >= 100.;Asthmatic patients part 2: Mild-moderate asthmatic patients will be selected using the following inclusion Age between 18 - 50 years at the screening visit History of episodic chest tightness and wheezing Controlled asthma according to the criteria by the Global Initiative for Asthma Non-smoking or stopped smoking more than 12 months ago and 80% of predicted Airway hyperresponsiveness, indicated by a positive acetyl-ß-methylcholine bromide (MeBr) challenge with PC20 3 mm;Control subjects: Age between 18 - 65 years at the screening visit Non-smoking or stopped smoking more than 12 months and 80% of predicted MeBr challenge with PC20 > 9.8 mg/ml Steroid-naïve or those participants who are currently not on corticosteroids and have not taken any corticosteroids by any dosing-routes within 8 weeks prior to the study Negative history of pulmonary or any other relevant diseases
Exclusion criteria
Exclusion criteria: For part 1 and 2: Women who are pregnant, lactating or have a positive urine pregnancy test at visit 1 Participation in any clinical investigational drug treatment protocol within the preceding 30 days Concomitant disease or condition which could interfere with the conduct of the study, or for which the treatment might interfere with the conduct of the study, or which would, in the opinion of the investigator, pose an unacceptable risk to the patient;Furthermore the following additional exclusion criteria will be used in part 2 of the study: RV16 titre > 1:6 in serum, measured at visit 1 History of clinical significant hypotensive episodes or symptoms of fainting, dizziness, or light-headedness Usage of high dose ICS (>500 µg/day to fluticasone or equivalent). Use of low or medium dose ICS (= 6 total PY Close contact with young children (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1 1. Determination of the different ILC populations in the lungs and peripheral blood of allergic and non-allergic asthma patients, both with high blood eosinophils and compare these to healthy non-allergic controls 2. Determination of the differences in innate cytokine production between bronchial epithelial cells from these groups, at baseline and after in vitro RV16 infection. 3. Study the interactions between ILCs and bronchial epithelial cells, DCs, B cells and eosinophils. Part 2 1. Investigate the effects of a RV16-induced exacerbation in asthmatics and healthy subjects on the proportion of the different pulmonary and peripheral blood ILC populations, as well as their activation and cytokine production. 2. Determination of the differences in innate cytokine production between bronchial epithelial cells from these groups, at baseline and after experimental RV16 infection. 3. Study the interaction between bronchial epithelial cells obtained before and after experimental RV16 infection and ILCs. | — |
Secondary
| Measure | Time frame |
|---|---|
| Part 1 1. Other immunological parameters, such as BAL cellular influx (neutrophils, eosinophils, basophils, T cells, B cells, macrophages, NK cells) and inflammatory mediator production. 2. Asses if the ILC populations in the lungs correlate with BAL cellular influx, inflammatory mediator production, lung function parameters. 3. Assess oxidative stress and cyto-protective responses in sputum supernatant and sputum macrophages. Part 2 1. Difference in maximum drop in FEV1, change in baseline morning or evening FEV1 on days 1-14 after RV16 challenge after RV16 infection between healthy and asthmatic subjects. 2. Effects on Asthma Control Diary (ACD) and Wisconsin Upper Respiratory Symptom Survey - 21 question version (WURSS-21). 3. Other immunological parameters, such as BAL cellular influx (neutrophils, eosinophils, basophils, T cells, B cells, macrophages, NK cells) and inflammatory mediator production. 4. Assess if the different ILC populations in the lungs after RV16 challenge correlate with clinical parameters, such as the maximum drop in FEV1, change in baseline morning or evening FEV1 on days 1-14 after RV16 challenge, ACD and WURSS-21. 5. Detection of RV16 specific B cells. 6. Assess oxidative stress and cyto-protective responses in sputum supernatant and sputum macrophages. | — |
Countries
Netherlands
Outcome results
None listed