The objective of the VIRCHILLD project is to identify age-related modifications of thebronchial epithelium physiology that account for differences in the response andsusceptibility to respiratory viruses. Epidemiology and cell-based data show thatrespiratory virus infections differentially affect children, adults or the elderlypopulations.The current worldwide pandemic of SARS-CoV-2 clearly highlighted this notion with a largepart of the deaths occurring in the elderly population and very few deaths amongstchildren. This may be linked to a decreased transmission and/or viral load withSARS-CoV-2 in children compared to adults and elderly. Less in the public eye is theobservation that other major respiratory virus targeting the bronchial epithelium (BE)such as rhinovirus (RV) and adenovirus (AdV) cause important clinical feature in childrenand have a much lower incidence in adults and the elderly populations, which is theopposite to the situation with SARS-CoV-2. Based on this remarkable discrepancy betweenrespiratory viruses the investigators hypothesize that intrinsic age-controlledproperties of the respiratory epithelium under resting physiological conditions determinevirus susceptibility and virus propagation.
The objective of the VIRCHILLD project is to identify age-related modifications of the
bronchial epithelium physiology able to explain differences in the response to
respiratory viruses. Several epidemiological and cell-based data have demonstrated that
respiratory virus infections differentially affect children, adults or the elderly
populations. Perhaps, this difference has been put most notably into the spotlight by the
current worldwide pandemic of SARS-CoV-2 with a large part of the deaths occurring in the
elderly population whereas very few deaths amongst children have been recorded. According
to some studies, this could be linked to a decreased transmission and/or viral load with
SARS-CoV-2 in children compared to adults and elderly. What is less in the public eye is
the observation that other major respiratory virus targeting the bronchial epithelium
such as rhinovirus and adenovirus cause important clinical feature in children and have a
much lower incidence in adults and the elderly populations, which is the opposite to the
situation with SARS-CoV-2. Based on this remarkable discrepancy between respiratory
viruses the investigators hypothesize that intrinsic age-controlled properties of the
respiratory epithelium under resting physiological conditions determines virus
susceptibility and virus propagation. Such hypothesis is supported by the literature and
our own strong preliminary data. A highly complementing consortium composed of experts in
lung physiology, pulmonary transcriptomic, respiratory viruses and ultrastructure
analysis will address the question. The investigators will use three major respiratory
pathogens (AdV, RV and SARS-CoV-2) to infect reconstituted fully functional respiratory
epithelium obtained from children, adults and elderly and study parameters of virus
infection and epithelial response. This project should highlight specific therapeutic
targets against respiratory viruses with a high prevalence in children such as rhinovirus
and adenoviruses to increase the therapeutic arsenal of clinician against those
infections.
Biological: SARS-CoV-2
Circulating strains of SARS-CoV-2 (including variants of concern) were already collected,
cultured and purified. The Wuhan reference strain will be used in the VIRCHILLD study to
infect cells.
Biological: Adenovirus (AdV)
Infection with C-type viruses (e.g. HAd-C5) using bronchial epithelium from adult donors
Biological: Rhinovirus
RV is a member of the picornaviridae family; small non-enveloped viruses with a single
strand positive RNA genome protected by an icosahedral capsid. They are divided in more
than 160 serotypes classed in subtype A, B and C. RV-A and RV-C infections will be used
in the VIRCHILLD study
Biological: No Intervention
no infection
Inclusion Criteria:
For pediatric patients requiring research-specific bronchial brushing:
- Child under 18 years old,
- Requiring bronchoscopy as part of routine care
- Having informed and signed consent from the holders of parental authority
For pediatric patients whose bronchial brushing will be carried out as part of their care
and for those whose surgical waste will be collected for research:
- Child under 18 years old,
- Requiring as part of routine care bronchoscopy and brushing or bronchial fibroscopy
under general anesthesia or surgical resection/lobectomy
- Having expressed their non-opposition to their child's participation in research
For adult patients:
- Man or woman
- Aged 18 or over
- Requiring as part of the care, thoracic surgery such as lobectomy, pneumonectomy or
lung transplantation in the Thoracic Surgery Department of Haut Lévêque du Chu
Hospital in Bordeaux or inclusion in the TUBE study, described below.
- having received an information note and not having objected to their participation
in the research
Exclusion Criteria:
- No affiliation or non-beneficiary of a social security system
- During a period of relative exclusion compared to another protocol
- Patient born before 36 weeks of amenorrhea
- Patient with a documented history of pulmonary fibrosis, primary pulmonary
hypertension, cystic fibrosis, pulmonary malformation or chronic viral infections
(hepatitis, HIV).
- Patient with any dental, nasopharyngeal or bronchial infection with fever (> 38°C)
requiring systemic antibiotics in the previous 4 weeks
Bordeaux University Hospital
Bordeaux, France
Investigator: Michael FAYON, MDPhD
michael.fayon@chu-bordeaux.fr
Investigator: Matthieu THUMEREL, MD
Thomas TRIAN, PhD
05 55 47 30 27 50
thomas.trian@u-bordeaux.fr
Aurore CAPELLI, PhD
0557820877
aurore.capelli@chu-bordeaux.fr
Michael FAYON, MDPhD, Principal Investigator
University Hospital, Bordeaux