1) to determine NETs-induced changes in ex vivo (RSV-infected) pediatric HAE (e.g. mucus hypersecretion and cell death) and 2) to explore pharmacological inhibition of NETs in this context.
ID
Source
Brief title
Condition
- Viral infectious disorders
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
We will use the collected cells to obtain pediatric HAE cultures. We will use
these cultures as an ex vivo model to study NETs induced changes in the context
of RSV infection of the pediatric airways. We will perform measurements on
airway mucus (protein expression) and airway epithelial damage (necrosis,
apoptosis, loss of differentiation, loss of barrier function, apoptotic gene
expression, inflammation markers and inflammatory pathways).
Secondary outcome
n.a.
Background summary
Viral lower respiratory tract infection (LRTI) caused by respiratory syncytial
virus (RSV) is an important cause of childhood morbidity and mortality
worldwide. Neutrophil recruitment and neutrophilic inflammation are hallmarks
in the pathophysiology of severe RSV-LRTI. There is accumulating evidence that
the formation of neutrophil extracellular traps (NETs) in the airways plays a
crucial role in the development of severe RSV-LRTI by contributing to mucus
plugging and epithelial injury. Therefore, NETs might be a potential target for
pharmacological intervention, making it imperative to gain insight into the
pathogenetic role of NETs formation in RSV-LRTI. Ex vivo three-dimensional (3D)
airway-modelling by the use of Human Airway Epithelial (HAE) cultures allows
the study of virus- epithelial airway cell interaction and immunopathology
without the use of modified cell lines or animals. However, there is a lack of
pediatric specific models. As RSV-LRTI specifically effects infants and the
mechanisms underlying respiratory insufficiency due to RSV-LRTI in young
children might differ from adults, it is important to develop a pediatric
airway model.
Study objective
1) to determine NETs-induced changes in ex vivo (RSV-infected) pediatric HAE
(e.g. mucus hypersecretion and cell death) and 2) to explore pharmacological
inhibition of NETs in this context.
Study design
single centre, ex -vivo laboratory study, designed to study NETs induced
changes in pediatric airway epithelial cells and airway mucus, with and without
RSV co-infection. We will use HAE cultures derived from infants, using a
minimally invasive procedure to obtain primary human, pediatric airway
epithelial cells. We will perform non - bronchoscopic bronchial cytobrushing
to obtain small lower airway epithelial cells for HAE culturing. This is an
extension with minor adaptions of a previous PICU study (MEC 06/097). Prior to
cytobrushing, patients are already endotracheally intubated for the elective
surgery by standard hospital procedures for elective surgery. Additionally, we
will test the obtained material for the presence of common respiratory tract
virusses (viral respiratory panel).
Study burden and risks
For ethical reasons, bronchoscopic procedures primarily for research purposes
are not justified in children. As an alternative, non-bronchoscopic
cytobrushing during elective surgery is considered to be an effective and safe
procedure in children. No serious risks or adverse events by non-bronchoscopic
cytobrushing have been reported. A previous clinical study by Bem1, carried out
in the Amsterdam Medical Center - location AMC, reported no adverse events.
The subjects of this study are minors and have no direct advantage of their
participation in this study. However, respiratory failure in RSV-LRTI is an
important cause of childhood hospitalization and research on the mechanisms
underlying respiratory failure in RSV-LRTI is therefore of benefit to this age
group, which we believe justifies our intended research project.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
- Age between 2 and 24 months
- No known pulmonary disease
- Endotracheal intubation (for elective surgery)
- No signs of infection (fever, temperature >38.5 C) and no respiratory
symptoms (cough, wheeze, snotty) present at moment of intubation.
- No reported respiratory symptoms in the last 7 days prior to surgery (cough,
wheeze, snotty)
- Informed consent obtained for both non-endoscopic cytobrushing and
serological testing after confirmation of comprehension of the Dutch language.
Exclusion criteria
- Age < 2 months or > 24 months
- Reported pulmonary disorder
- Non-elective endotracheally intubation
- Symptoms of a present or recent infection (T>38.5C in the last 7 days prior
to surgery) or reported respiratory symptoms in the last 7 days prior to
surgery
- No consent.
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 | NL71577.018.19 |