To examine the apoptotic response of isolated and cultured airway epithelial cells of infants to a wide variety of cytotoxic agents and potential apoptotic stimulants ex vivo. These include oxygen, nitric oxide, peroxynitrite, cigarette smoke…
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Evidence for apoptosis: caspase-3 activity, annexin-V binding and morphological
studies.
Apoptotic pathways: RNA of the Bcl-2 and IAP family of pro- and anti-apoptotic
factors, RNA and protein analysis of Fas/FasL and caspase-8 and -9 activity.
Secondary outcome
none
Background summary
Apoptosis, a form of programmed cell death, plays a key role in many human
disorders. In addition, it is an essential process during organogenesis,
including the development and maturation of the lung after birth. Disruption of
the tight regulation of apoptosis in the lungs of infants and young children
may therefore contribute to both short and long term organ dysfunction. It has
been shown that exposure to several environmental factors (under which oxygen
and nitrogen radicals), but also viral and bacterial respiratory pathogens
leads to a higher extent of apoptosis of the respiratory epithelium. There is
however, limited knowledge about the effects of this on the developing and
maturing lungs and airway of young children.
The extent of apoptotic reactions in the lung of children upon exposure to
these factors is very likely different in comparison to adults. In addition,
these factors may also lead to disruption of the normal development and
maturation of the respiratory system with the abovementioned consequences for
lung function. In this study we propose to perform ex vivo experiments with
isolated and cultured airway epithelial cells of infants on this subject.
Study objective
To examine the apoptotic response of isolated and cultured airway epithelial
cells of infants to a wide variety of cytotoxic agents and potential apoptotic
stimulants ex vivo. These include oxygen, nitric oxide, peroxynitrite,
cigarette smoke extract and viral and bacterial respiratory pathogens.
In addition, we aim to investigate the influence of (sex) hormone status and
differences with adult airway epithelial cells.
Study design
Observational study ex vivo.
Study burden and risks
Sample collection will be performed by non-bronchoscopic bronchial
cytobrushing, performed immediately after endotracheal intubation, before start
of the elective surgical procedure. In addition 2 ml blood will be collected
from an arterial or venous catheter for serologic testing for human respiratory
viruses. Based on the existing literature no complications of any kind are
expected from the sample collection procedures and patient burden will be
minimal.
Because this study focuses on the regulation of apoptosis of the respiratory
epithelium of children only subjects in the specified age group can be
included. The subjects have no direct potential benefit of participation, but
the results of this study are beneficial to children in this age group in
general.
Postbus 22660
1100 DD
Nederland
Postbus 22660
1100 DD
Nederland
Listed location countries
Age
Inclusion criteria
Age: 2 - 24 months.
Endotracheally intubated for elective surgery for non-pulmonary disorders at the Academic Medical Center in Amsterdam.
Exclusion criteria
Age under 2- or above 24 months.
History of pulmonary disorder.
No permission form parents or guardian.
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 |
|---|---|
| CCMO | NL12124.018.06 |