This study aims to determine whether the ILC populations differ in the lungs of COPD patients, who differ with respect to COPD severity, and healthy subjects and how these cells are regulated by bronchial epithelial cells. Furthermore we want to…
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Part 1
1. Investigate the effects of a RV16-induced exacerbation in COPD patients 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.
Part 2
1. Determination of the different ILC populations in the lungs and peripheral
blood of COPD patients, who differ with respect in COPD severity, and compare
these to healthy controls without COPD/asthma.
2. Study the interactions between ILCs and bronchial epithelial cells and other
local cells.
Secondary outcome
Part 1
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
COPD patients.
2. Effects on two questionnaires for COPD symptoms
(http://www.catestonline.org/english/indexEN.htm and as described in Mallia P,
et al. Experimental rhinovirus infection as a human model of chronic
obstructive pulmonary disease exacerbation. Am J Respir Crit Care Med. 2011 Mar
15;183(6):734-42).
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, and
questionnaires.
5. Assess oxidative stress and cyto-protective responses in sputum supernatant
and sputum macrophages.
Part 2
1. Asses T lymphocytes and NK cells in blood and lung tissue from patients and
controls.
Background summary
COPD is a chronic lung inflammatory disorder defined by irreversible and
progressive airflow obstruction. Severity of COPD ranges from mild to severe
(GOLD I - IV). Importantly, progression of this disease has been linked to
exacerbation frequency. Acute exacerbations in COPD are typically associated
with viral infections, predominantly rhinovirus. Frequent exacerbations not
only accelerate disease, but impair quality of life, increase the risk of
hospitalization and are the major cause of mortality and morbidity in these
patients. The mechanisms underlying virus-induced exacerbations are still far
from clear. Innate Lymphoid Cells (ILCs) represent a novel subset of immune
cells that have recently been described to play critical roles in allergic
asthma, helminth infections, colitis/IBD, anatomical containment of commensal
bacteria, and tissue remodeling following injury or infection. Preliminary
findings suggest that ILC2 and ILC3 populations are significantly reduced in
COPD patients while there is a corresponding increase in the ILC1 subset. Human
bronchial epithelial cells are the major cell type infected by RV in the lower
respiratory tract in vivo and are capable of driving ILC plasticity.
Study objective
This study aims to determine whether the ILC populations differ in the lungs of
COPD patients, who differ with respect to COPD severity, and healthy subjects
and how these cells are regulated by bronchial epithelial cells. Furthermore we
want to study how this is affected by rhinovirus infection.
Study design
Part 1:
After screening the participants will undergo 2 bronchoscopies. During the
bronchoscopy a lavage will be done, an epithelial brush and 6 biopsies will be
taken. This will be done 5 days before and 2 days after infection with RV16.
Moreover blood will be drawn on day -14, 2, 6, 14 and 6-8 weeks after RV16 and
lung function tests will be done. On day -1 and 6 a sputum induction will be
performed.
Part 2:
After screening blood will be drawn once just before or after lung resection.
Intervention
In part 1 all participants will undergo a RV16 infection.
Study burden and risks
Part 1:
8 visits, 5x blood sampling, 5x lung function tests and 2x bronchoscopy, 2x
sputum induction, 1x RV16 infection and during 3 weeks daily
recording of common cold and COPD scores and their FEV1 in a diary.
The bronchoscopy, with a lavage, brushes and biopsies, is an invasive procedure
that- even though lidocaine anaesthesia is applied- can be unpleasant and can
induce dry cough and a sore throat. According to the standard operating
procedure from Endoscopy a midazolam/propofol conscious sedation will be given
to minimize discomfort. The brushing of the airways and the biopsies can give
rise to a superficial bleeding which usually stops rapidly.
The experimental infection with RV16 will induce common cold complaints,
probably to a lesser extend in the healthy volunteers. RV16 infection can
exacerbate COPD symptoms.
Part 2:
1x blood sampling
Meibergdreef 9 K0-150
1105 AZ Amsterdam 1105 AZ
NL
Meibergdreef 9 K0-150
1105 AZ Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
For rhinovirus challenges, patients
* non-smoking, or ex-smoking (*1 years ago), *10 pack years; GOLD stage II (post bronchodilator FEV1 <80% predicted and FEV1/FVC <70%)
* Allowed COPD specific medication: LABA and LAMA medication will be allowed, but no ICS
* Have no history of bronchiectasis, lung cancer or other significant respiratory disease.
* Be stable on COPD medication, no exacerbation or changes in COPD medication in the past 6 weeks. ;The age- and smoking history-matched controls will be extensively characterized with respect to lung function, medication and medical history. They have to:
* Be non-smoking, or ex-smoking (*1 years ago)
* Have no respiratory diagnosis of asthma or COPD
* Have no history of bronchiectasis, lung cancer or other significant respiratory disease.;For the COPD patients not challenged with rhinovirus:
* non-smoking, or ex-smoking (*2 years ago), GOLD I, II, IV
* no history of bronchiectasis, lung cancer or other significant respiratory disease;Non-COPD control group, not challenged with rhinovirus:
* Be non-smoking, or ex-smoking (*2 years ago), apart from those belonging to the controls who smoke
* Have no respiratory diagnosis of asthma or COPD
Exclusion criteria
For rhinovirus challenges,
* Women who are pregnant, lactating or have a positive urine pregnancy test at visit 1
* RV16 titre > 1:6 in serum, measured at visit 1
* Has had any acute illness, including a common cold, within 4 weeks prior to visit 1
* Close contact with young children (< 2 years)
* Has donated blood or has had a blood loss of more than 450 mL within 60 days prior to screening visit 1 or plans to donate blood during the study;For the patients not challenged with rhinovirus:
* 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
Design
Recruitment
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 |
|---|---|
| CCMO | NL52194.018.15 |
| Other | NTR zal worden aangevraagd |