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

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)