Virus and Bronchial Epithelium in Children and the Elderly (VIRCHILLD)

U

University Hospital of Bordeaux

Status

Enrolling

Conditions

SARS-CoV-2

Treatments

Biological: Adenovirus (AdV)
Biological: Rhinovirus
Biological: SARS-CoV-2
Biological: No Intervention

Study type

Interventional

Funder types

Other

Identifiers

NCT06224062
CHUBX 2021/43

Details and patient eligibility

About

The objective of the VIRCHILLD project is to identify age-related modifications of the bronchial epithelium physiology that account for differences in the response and susceptibility to respiratory viruses. Epidemiology and cell-based data show that respiratory virus infections differentially affect children, adults or the elderly populations. The current worldwide pandemic of SARS-CoV-2 clearly highlighted this notion with a large part of the deaths occurring in the elderly population and very few deaths amongst children. This may be linked to a decreased transmission and/or viral load with SARS-CoV-2 in children compared to adults and elderly. Less in the public eye is the observation that other major respiratory virus targeting the bronchial epithelium (BE) such as rhinovirus (RV) and adenovirus (AdV) 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 determine virus susceptibility and virus propagation.

Full description

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.

Enrollment

200 estimated patients

Sex

All

Ages

Under 17 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Basic Science

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

200 participants in 3 patient groups

children
Experimental group
Description:
reconstituted fully functional respiratory epithelium obtained from children (0 -18 years old)
Treatment:
Biological: No Intervention
Biological: SARS-CoV-2
Biological: Rhinovirus
Biological: Adenovirus (AdV)
adults
Experimental group
Description:
reconstituted fully functional respiratory epithelium obtained from adults (18 to 60 years old)
Treatment:
Biological: No Intervention
Biological: SARS-CoV-2
Biological: Rhinovirus
Biological: Adenovirus (AdV)
elderly
Experimental group
Description:
reconstituted fully functional respiratory epithelium obtained from adults (over 60 years old)
Treatment:
Biological: No Intervention
Biological: SARS-CoV-2
Biological: Rhinovirus
Biological: Adenovirus (AdV)

Trial contacts and locations

1

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Central trial contact

Aurore CAPELLI, PhD; Thomas TRIAN, PhD

Data sourced from clinicaltrials.gov

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